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Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

General Review Article

Molecular Signaling Pathways and Essential Metabolic Elements in Bone Remodeling: An Implication of Therapeutic Targets for Bone Diseases

Author(s): Aditi Sharma, Lalit Sharma and Rohit Goyal*

Volume 22 , Issue 1 , 2021

Published on: 10 September, 2020

Page: [77 - 104] Pages: 28

DOI: 10.2174/1389450121666200910160404

Price: $65

Abstract

Bone is one of the dynamic tissues in the human body that undergoes continuous remodelling through subsequent actions of bone cells, osteoclasts, and osteoblasts. Several signal transduction pathways are involved in the transition of mesenchymal stem cells into osteoblasts. These primarily include Runx2, ATF4, Wnt signaling and sympathetic signalling. The differentiation of osteoclasts is controlled by M-CSF, RANKL, and costimulatory signalling. It is well known that bone remodelling is regulated through receptor activator of nuclear factor-kappa B ligand followed by binding to RANK, which eventually induces the differentiation of osteoclasts. The resorbing osteoclasts secrete TRAP, cathepsin K, MMP-9 and gelatinase to digest the proteinaceous matrix of type I collagen and form a saucer-shaped lacuna along with resorption tunnels in the trabecular bone. Osteoblasts secrete a soluble decoy receptor, osteoprotegerin that prevents the binding of RANK/RANKL and thus moderating osteoclastogenesis.

Moreover, bone homeostasis is also regulated by several growth factors like, cytokines, calciotropic hormones, parathyroid hormone and sex steroids. The current review presents a correlation of the probable molecular targets underlying the regulation of bone mass and the role of essential metabolic elements in bone remodelling. Targeting these signaling pathways may help to design newer therapies for treating bone diseases.

Keywords: Bone, osteoblast, osteoclast, RANK, molecular signaling, estrogen.

Graphical Abstract
[1]
Florencio-Silva R, Sasso GR, Sasso-Cerri E, Simões MJ, Cerri PS. Biology of bone tissue: structure, function, and factors that influence bone cells. BioMed Res Int 2015; 2015: 421746.
[http://dx.doi.org/10.1155/2015/421746] [PMID: 26247020]
[2]
Sun W, Zhao C, Li Y, et al. Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity. Cell Discov 2016; 2: 16015.
[http://dx.doi.org/10.1038/celldisc.2016.15] [PMID: 27462462]
[3]
Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med 2006; 354(21): 2250-61.
[http://dx.doi.org/10.1056/NEJMra053077] [PMID: 16723616]
[4]
Roodman GD. Cell biology of the osteoclast. Exp Hematol 1999; 27(8): 1229-41.
[http://dx.doi.org/10.1016/S0301-472X(99)00061-2] [PMID: 10428500]
[5]
Winkler DG, Sutherland MK, Geoghegan JC, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J 2003; 22(23): 6267-76.
[http://dx.doi.org/10.1093/emboj/cdg599] [PMID: 14633986]
[6]
Visconti R, Iversen T, Cottrell JA. Review of Dysregulated Osteoblast and Osteoclast Coupling in Bone Disease and Failure. J Bone Res 2019; 7(201): 1-14.
[7]
Liang H, Yu F, Tong Z, Huang Z. Effect of Cistanches Herba aqueous extract on bone loss in ovariectomized rat. Int J Mol Sci 2011; 12(8): 5060-9.
[http://dx.doi.org/10.3390/ijms12085060] [PMID: 21954345]
[8]
Weivoda MM, Chew CK, Monroe DG, et al. Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism. Nat Commun 2020; 11(1): 87.
[http://dx.doi.org/10.1038/s41467-019-14003-6] [PMID: 31911667]
[9]
Ahuja K, Sen S, Dhanwal D. Risk factors and epidemiological profile of hip fractures in Indian population: A case-control study. Osteoporos Sarcopenia 2017; 3(3): 138-48.
[http://dx.doi.org/10.1016/j.afos.2017.08.097] [PMID: 30775519]
[10]
Nguyen ND, Ahlborg HG, Center JR, Eisman JA, Nguyen TV. Residual lifetime risk of fractures in women and men. J Bone Miner Res 2007; 22(6): 781-8.
[http://dx.doi.org/10.1359/jbmr.070315] [PMID: 17352657]
[11]
Bianchi ML, Orsini MR, Saraifoger S, Ortolani S, Radaelli G, Betti S. Quality of life in post-menopausal osteoporosis. Health Qual Life Outcomes 2005; 3: 78.
[http://dx.doi.org/10.1186/1477-7525-3-78] [PMID: 16321148]
[12]
Chan CKY, Mason A, Cooper C, Dennison E. Novel advances in the treatment of osteoporosis. Br Med Bull 2016; 119(1): 129-42.
[http://dx.doi.org/10.1093/bmb/ldw033] [PMID: 27558130]
[13]
Capulli M, Paone R, Rucci N. Osteoblast and osteocyte: games without frontiers. Arch Biochem Biophys 2014; 561: 3-12.
[http://dx.doi.org/10.1016/j.abb.2014.05.003] [PMID: 24832390]
[14]
Nakashima K, Zhou X, Kunkel G, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 2002; 108(1): 17-29.
[http://dx.doi.org/10.1016/S0092-8674(01)00622-5] [PMID: 11792318]
[15]
Takahashi N, Udagawa N, Takami M, Suda T. Principles of Bone Biology. Academic Press San Diego 2002; pp. 109-26.
[16]
Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 2000; 21(2): 115-37.
[PMID: 10782361]
[17]
Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997; 89(5): 747-54.
[http://dx.doi.org/10.1016/S0092-8674(00)80257-3] [PMID: 9182762]
[18]
Kawane T, Komori H, Liu W, et al. Dlx5 and mef2 regulate a novel runx2 enhancer for osteoblast-specific expression. J Bone Miner Res 2014; 29(9): 1960-9.
[http://dx.doi.org/10.1002/jbmr.2240] [PMID: 24692107]
[19]
Liu W, Toyosawa S, Furuichi T, et al. Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures. J Cell Biol 2001; 155(1): 157-66.
[http://dx.doi.org/10.1083/jcb.200105052] [PMID: 11581292]
[20]
Jensen ED, Gopalakrishnan R, Westendorf JJ. Regulation of gene expression in osteoblasts. Biofactors 2010; 36(1): 25-32.
[PMID: 20087883]
[21]
Celil AB, Campbell PG. BMP-2 and insulin-like growth factor-I mediate Osterix (Osx) expression in human mesenchymal stem cells via the MAPK and protein kinase D signaling pathways. J Biol Chem 2005; 280(36): 31353-9.
[http://dx.doi.org/10.1074/jbc.M503845200] [PMID: 16000303]
[22]
Karsenty G. Bone formation and factors affecting this process. Matrix Biol 2000; 19(2): 85-9.
[http://dx.doi.org/10.1016/S0945-053X(00)00053-6] [PMID: 10842091]
[23]
Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell 2012; 149(6): 1192-205.
[http://dx.doi.org/10.1016/j.cell.2012.05.012] [PMID: 22682243]
[24]
Yu S, Zhu K, Lai Y, et al. ATF4 promotes β-catenin expression and osteoblastic differentiation of bone marrow mesenchymal stem cells. Int J Biol Sci 2013; 9(3): 256-66.
[http://dx.doi.org/10.7150/ijbs.5898] [PMID: 23494915]
[25]
Elefteriou F, Campbell P, Ma Y. Control of bone remodeling by the peripheral sympathetic nervous system. Calcif Tissue Int 2014; 94(1): 140-51.
[http://dx.doi.org/10.1007/s00223-013-9752-4] [PMID: 23765388]
[26]
Yu S, Franceschi RT, Luo M, et al. Critical role of activating transcription factor 4 in the anabolic actions of parathyroid hormone in bone. PLoS One 2009; 4(10): e7583.
[http://dx.doi.org/10.1371/journal.pone.0007583] [PMID: 19851510]
[27]
Hinoi E, Fujimori S, Takarada T, Taniura H, Yoneda Y. Facilitation of glutamate release by ionotropic glutamate receptors in osteoblasts. Biochem Biophys Res Commun 2002; 297(3): 452-8.
[http://dx.doi.org/10.1016/S0006-291X(02)02223-4] [PMID: 12270113]
[28]
Väänänen HK, Zhao H, Mulari M, Halleen JM. The cell biology of osteoclast function. J Cell Sci 2000; 113(Pt 3): 377-81.
[PMID: 10639325]
[29]
Itzstein C, Coxon FP, Rogers MJ. The regulation of osteoclast function and bone resorption by small GTPases. Small GTPases 2011; 2(3): 117-30.
[http://dx.doi.org/10.4161/sgtp.2.3.16453] [PMID: 21776413]
[30]
Arnett T. Bone Structure and Function: Organization composition of bone, bone modelling and remodelling, bone cells. 43rd Annual European Calcified Tissue Society Congress BioScientifica. 5: 336-8.
[31]
Al Quobaili F, Montenarh M. CK2 and the regulation of the carbohydrate metabolism. Metabolism 2012; 61(11): 1512-7.
[http://dx.doi.org/10.1016/j.metabol.2012.07.011] [PMID: 22917893]
[32]
Ahmad KA, Wang G, Unger G, Slaton J, Ahmed K. Protein kinase CK2--a key suppressor of apoptosis. Adv Enzyme Regul 2008; 48: 179-87.
[http://dx.doi.org/10.1016/j.advenzreg.2008.04.002] [PMID: 18492491]
[33]
Duncan JS, Litchfield DW. Too much of a good thing: the role of protein kinase CK2 in tumorigenesis and prospects for therapeutic inhibition of CK2. Biochim Biophys Acta 2008; 1784(1): 33-47.
[http://dx.doi.org/10.1016/j.bbapap.2007.08.017] [PMID: 17931986]
[34]
Faust M, Montenarh M. Subcellular localization of protein kinase CK2. A key to its function? Cell Tissue Res 2000; 301(3): 329-40.
[http://dx.doi.org/10.1007/s004410000256] [PMID: 10994779]
[35]
Turgeman G, Zilberman Y, Zhou S, et al. Systemically administered rhBMP-2 promotes MSC activity and reverses bone and cartilage loss in osteopenic mice. J Cell Biochem 2002; 86(3): 461-74.
[http://dx.doi.org/10.1002/jcb.10231] [PMID: 12210753]
[36]
Bragdon B, Moseychuk O, Saldanha S, King D, Julian J, Nohe A. Bone morphogenetic proteins: a critical review. Cell Signal 2011; 23(4): 609-20.
[http://dx.doi.org/10.1016/j.cellsig.2010.10.003] [PMID: 20959140]
[37]
Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors 2004; 22(4): 233-41.
[http://dx.doi.org/10.1080/08977190412331279890] [PMID: 15621726]
[38]
Bragdon B, Thinakaran S, Moseychuk O, et al. Casein kinase 2 beta-subunit is a regulator of bone morphogenetic protein 2 signaling. Biophys J 2010; 99(3): 897-904.
[http://dx.doi.org/10.1016/j.bpj.2010.04.070] [PMID: 20682268]
[39]
Bragdon B, Thinakaran S, Moseychuk O, et al. Casein kinase 2 regulates in vivo bone formation through its interaction with bone morphogenetic protein receptor type Ia. Bone 2011; 49(5): 944-54.
[http://dx.doi.org/10.1016/j.bone.2011.06.037] [PMID: 21763800]
[40]
Son YH, Moon SH, Kim J. The protein kinase 2 inhibitor CX-4945 regulates osteoclast and osteoblast differentiation in vitro. Mol Cells 2013; 36(5): 417-23.
[http://dx.doi.org/10.1007/s10059-013-0184-9] [PMID: 24293011]
[41]
Vrathasha V, Weidner H, Nohe A. Mechanism of CK2.3, a Novel Mimetic Peptide of Bone Morphogenetic Protein Receptor Type IA, Mediated Osteogenesis. Int J Mol Sci 2019; 20(10): 1-27.
[http://dx.doi.org/10.3390/ijms20102500] [PMID: 31117181]
[42]
Götz C, Montenarh M. Protein kinase CK2 in development and differentiation. Biomed Rep 2017; 6(2): 127-33.
[http://dx.doi.org/10.3892/br.2016.829] [PMID: 28357063]
[43]
Wittkowske C, Reilly GC, Lacroix D, Perrault CM. In Vitro bone cell models: impact of fluid shear stress on bone formation. Front Bioeng Biotechnol 2016; 4: 87.
[http://dx.doi.org/10.3389/fbioe.2016.00087] [PMID: 27896266]
[44]
Kadler KE, Hill A, Canty-Laird EG. Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators. Curr Opin Cell Biol 2008; 20(5): 495-501.
[http://dx.doi.org/10.1016/j.ceb.2008.06.008] [PMID: 18640274]
[45]
Eriksen EF. Cellular mechanisms of bone remodeling. Rev Endocr Metab Disord 2010; 11(4): 219-27.
[http://dx.doi.org/10.1007/s11154-010-9153-1] [PMID: 21188536]
[46]
Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem 2010; 285(33): 25103-8.
[http://dx.doi.org/10.1074/jbc.R109.041087] [PMID: 20501658]
[47]
Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res 2000; 15(1): 2-12.
[http://dx.doi.org/10.1359/jbmr.2000.15.1.2] [PMID: 10646108]
[48]
Darnay BG, Haridas V, Ni J, Moore PA, Aggarwal BB. Characterization of the intracellular domain of receptor activator of NF-kappaB (RANK). Interaction with tumor necrosis factor receptor-associated factors and activation of NF-kappab and c-Jun N-terminal kinase. J Biol Chem 1998; 273(32): 20551-5.
[http://dx.doi.org/10.1074/jbc.273.32.20551] [PMID: 9685412]
[49]
Naito A, Azuma S, Tanaka S, et al. Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells 1999; 4(6): 353-62.
[http://dx.doi.org/10.1046/j.1365-2443.1999.00265.x] [PMID: 10421844]
[50]
Gohda J, Akiyama T, Koga T, Takayanagi H, Tanaka S, Inoue J. RANK-mediated amplification of TRAF6 signaling leads to NFATc1 induction during osteoclastogenesis. EMBO J 2005; 24(4): 790-9.
[http://dx.doi.org/10.1038/sj.emboj.7600564] [PMID: 15678102]
[51]
Wong BR, Besser D, Kim N, et al. TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol Cell 1999; 4(6): 1041-9.
[http://dx.doi.org/10.1016/S1097-2765(00)80232-4] [PMID: 10635328]
[52]
Takayanagi H, Ogasawara K, Hida S, et al. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-γ. Nature 2000; 408(6812): 600-5.
[http://dx.doi.org/10.1038/35046102] [PMID: 11117749]
[53]
Takayanagi H. The role of NFAT in osteoclast formation. Ann N Y Acad Sci 2007; 1116: 227-37.
[http://dx.doi.org/10.1196/annals.1402.071] [PMID: 18083930]
[54]
Takatsuna H, Asagiri M, Kubota T, et al. Inhibition of RANKL-induced osteoclastogenesis by (-)-DHMEQ, a novel NF-kappaB inhibitor, through downregulation of NFATc1. J Bone Miner Res 2005; 20(4): 653-62.
[http://dx.doi.org/10.1359/JBMR.041213] [PMID: 15765185]
[55]
Yavropoulou MP, Yovos JG. Osteoclastogenesis current knowledge and future perspectives. J Musculoskelet Neuronal Interact 2008; 8(3): 204-16.
[PMID: 18799853]
[56]
Kim JH, Kim N. Regulation of NFATc1 in Osteoclast Differentiation. J Bone Metab 2014; 21(4): 233-41.
[http://dx.doi.org/10.11005/jbm.2014.21.4.233] [PMID: 25489571]
[57]
Wang ZQ, Ovitt C, Grigoriadis AE, Möhle-Steinlein U, Rüther U, Wagner EF. Bone and haematopoietic defects in mice lacking c-fos. Nature 1992; 360(6406): 741-5.
[http://dx.doi.org/10.1038/360741a0] [PMID: 1465144]
[58]
Gazon H, Barbeau B, Mesnard JM, Peloponese JM Jr. Hijacking of the AP-1 Signaling Pathway during Development of ATL. Front Microbiol 2018; 8: 2686.
[http://dx.doi.org/10.3389/fmicb.2017.02686] [PMID: 29379481]
[59]
Takayanagi H, Kim S, Matsuo K, et al. RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta. Nature 2002; 416(6882): 744-9.
[http://dx.doi.org/10.1038/416744a] [PMID: 11961557]
[60]
Huang W, Yang S, Shao J, Li YP. Signaling and transcriptional regulation in osteoblast commitment and differentiation. Front Biosci 2007; 12: 3068-92.
[http://dx.doi.org/10.2741/2296] [PMID: 17485283]
[61]
Chabadel A, Rodri guez BD, Rudkin BB, Haller BW, Genot E. Integrin organize two functionally distinct actin domains in osteoclasts. Mol Biol Cell 2007; 18: 4899-910.
[http://dx.doi.org/10.1091/mbc.e07-04-0378] [PMID: 17898081]
[62]
Shinohara M, Koga T, Okamoto K, et al. Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. Cell 2008; 132(5): 794-806.
[http://dx.doi.org/10.1016/j.cell.2007.12.037] [PMID: 18329366]
[63]
Zhang K, Barragan-Adjemian C, Ye L, et al. E11/gp38 selective expression in osteocytes: regulation by mechanical strain and role in dendrite elongation. Mol Cell Biol 2006; 26(12): 4539-52.
[http://dx.doi.org/10.1128/MCB.02120-05] [PMID: 16738320]
[64]
Deel MD, Li JJ, Crose LE, Linardic CMA. A Review: Molecular Aberrations within Hippo Signaling in Bone and Soft-Tissue Sarcomas. Front Oncol 2015; 5: 190.
[http://dx.doi.org/10.3389/fonc.2015.00190] [PMID: 26389076]
[65]
Byun MR, Hwang JH, Kim AR, et al. Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation. Cell Death Differ 2014; 21(6): 854-63.
[http://dx.doi.org/10.1038/cdd.2014.8] [PMID: 24510127]
[66]
Dupont S, Morsut L, Aragona M, et al. Role of YAP/TAZ in mechanotransduction. Nature 2011; 474(7350): 179-83.
[http://dx.doi.org/10.1038/nature10137] [PMID: 21654799]
[67]
Hansen CG, Moroishi T, Guan KL. YAP and TAZ: a nexus for Hippo signaling and beyond. Trends Cell Biol 2015; 25(9): 499-513.
[http://dx.doi.org/10.1016/j.tcb.2015.05.002] [PMID: 26045258]
[68]
Liu H, Jiang D, Chi F, Zhao B. The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation. Protein Cell 2012; 3(4): 291-304.
[http://dx.doi.org/10.1007/s13238-012-2919-3] [PMID: 22549587]
[69]
Xiang L, Yu H, Zhang X, et al. The versatile hippo pathway in oral-maxillofacial development and bone remodeling. Dev Biol 2018; 440(2): 53-63.
[http://dx.doi.org/10.1016/j.ydbio.2018.05.017] [PMID: 29792855]
[70]
Wrighton KH. Mechanotransduction: YAP and TAZ feel the force. Nat Rev Mol Cell Biol 2011; 12(7): 404.
[http://dx.doi.org/10.1038/nrm3136] [PMID: 21673726]
[71]
Chan SW, Lim CJ, Chen L, et al. The Hippo pathway in biological control and cancer development. J Cell Physiol 2011; 226(4): 928-39.
[http://dx.doi.org/10.1002/jcp.22435] [PMID: 20945341]
[72]
Kanai F, Marignani PA, Sarbassova D, et al. TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins. EMBO J 2000; 19(24): 6778-91.
[http://dx.doi.org/10.1093/emboj/19.24.6778] [PMID: 11118213]
[73]
Li C, Wang S, Xing Z, et al. A ROR1-HER3-lncRNA signalling axis modulates the Hippo-YAP pathway to regulate bone metastasis. Nat Cell Biol 2017; 19(2): 106-19.
[http://dx.doi.org/10.1038/ncb3464] [PMID: 28114269]
[74]
Zhao B, Ye X, Yu J, et al. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev 2008; 22(14): 1962-71.
[http://dx.doi.org/10.1101/gad.1664408] [PMID: 18579750]
[75]
Tsika RW, Schramm C, Simmer G, Fitzsimons DP, Moss RL, Ji J. Overexpression of TEAD-1 in transgenic mouse striated muscles produces a slower skeletal muscle contractile phenotype. J Biol Chem 2008; 283(52): 36154-67.
[http://dx.doi.org/10.1074/jbc.M807461200] [PMID: 18978355]
[76]
Zanconato F, Forcato M, Battilana G, et al. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat Cell Biol 2015; 17(9): 1218-27.
[http://dx.doi.org/10.1038/ncb3216] [PMID: 26258633]
[77]
Hong JH, Hwang ES, McManus MT, et al. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science 2005; 309(5737): 1074-8.
[http://dx.doi.org/10.1126/science.1110955] [PMID: 16099986]
[78]
Liu X, Li H, Rajurkar M, et al. Tead and AP1 Coordinate Transcription and Motility. Cell Rep 2016; 14(5): 1169-80.
[http://dx.doi.org/10.1016/j.celrep.2015.12.104] [PMID: 26832411]
[79]
Xia W, Liu Y, Jiao J. GRM7 regulates embryonic neurogenesis via CREB and YAP. Stem Cell Reports 2015; 4(5): 795-810.
[http://dx.doi.org/10.1016/j.stemcr.2015.03.004] [PMID: 25921811]
[80]
Scheel H, Hofmann K. A novel interaction motif, SARAH, connects three classes of tumor suppressor. Curr Biol 2003; 13(23): R899-900.
[http://dx.doi.org/10.1016/j.cub.2003.11.007] [PMID: 14654011]
[81]
Gladden AB, Hebert AM, Schneeberger EE, McClatchey AI. The NF2 tumor suppressor, Merlin, regulates epidermal development through the establishment of a junctional polarity complex. Dev Cell 2010; 19(5): 727-39.
[http://dx.doi.org/10.1016/j.devcel.2010.10.008] [PMID: 21074722]
[82]
Das Thakur M, Feng Y, Jagannathan R, Seppa MJ, Skeath JB, Longmore GD. Ajuba LIM proteins are negative regulators of the Hippo signaling pathway. Curr Biol 2010; 20(7): 657-62.
[http://dx.doi.org/10.1016/j.cub.2010.02.035] [PMID: 20303269]
[83]
Yang W, Han W, Qin A, Wang Z, Xu J, Qian Y. The emerging role of Hippo signaling pathway in regulating osteoclast formation. J Cell Physiol 2018; 233(6): 4606-17.
[http://dx.doi.org/10.1002/jcp.26372] [PMID: 29219182]
[84]
Tanaka-Kamioka K, Kamioka H, Ris H, Lim SS. Osteocyte shape is dependent on actin filaments and osteocyte processes are unique actin-rich projections. J Bone Miner Res 1998; 13(10): 1555-68.
[http://dx.doi.org/10.1359/jbmr.1998.13.10.1555] [PMID: 9783544]
[85]
Kamioka H, Sugawara Y, Honjo T, Yamashiro T, Takano-Yamamoto T. Terminal differentiation of osteoblasts to osteocytes is accompanied by dramatic changes in the distribution of actin-binding proteins. J Bone Miner Res 2004; 19(3): 471-8.
[http://dx.doi.org/10.1359/JBMR.040128] [PMID: 15040836]
[86]
Bellido T, Plotkin LI, Bruzzaniti A. Bone cells, Basic and Applied Bone Biology. Elsevier 2014; pp. 27-45.
[87]
Plotkin LI, Bellido T. Beyond gap junctions: Connexin43 and bone cell signaling. Bone 2013; 52(1): 157-66.
[http://dx.doi.org/10.1016/j.bone.2012.09.030] [PMID: 23041511]
[88]
Plotkin LI, Manolagas SC, Bellido T. Transduction of cell survival signals by connexin-43 hemichannels. J Biol Chem 2002; 277(10): 8648-57.
[http://dx.doi.org/10.1074/jbc.M108625200] [PMID: 11741942]
[89]
Bonewald LF. The amazing osteocyte. J Bone Miner Res 2011; 26(2): 229-38.
[http://dx.doi.org/10.1002/jbmr.320] [PMID: 21254230]
[90]
Shimada T, Mizutani S, Muto T, et al. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA 2001; 98(11): 6500-5.
[http://dx.doi.org/10.1073/pnas.101545198] [PMID: 11344269]
[91]
Genetos DC, Kephart CJ, Zhang Y, Yellowley CE, Donahue HJ. Oscillating fluid flow activation of gap junction hemichannels induces ATP release from MLO-Y4 osteocytes. J Cell Physiol 2007; 212(1): 207-14.
[http://dx.doi.org/10.1002/jcp.21021] [PMID: 17301958]
[92]
Lu XL, Huo B, Park M, Guo XE. Calcium response in osteocytic networks under steady and oscillatory fluid flow. Bone 2012; 51(3): 466-73.
[http://dx.doi.org/10.1016/j.bone.2012.05.021] [PMID: 22750013]
[93]
Torre E. Molecular signaling mechanisms behind polyphenol-induced bone anabolism. Phytochem Rev 2017; 16(6): 1183-226.
[http://dx.doi.org/10.1007/s11101-017-9529-x] [PMID: 29200988]
[94]
Poole KES, van Bezooijen RL, Loveridge N, et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J 2005; 19(13): 1842-4.
[http://dx.doi.org/10.1096/fj.05-4221fje] [PMID: 16123173]
[95]
Metzger CE, Narayanan A, Zawieja DC, Bloomfield SA. Inflammatory bowel disease in a rodent model alters osteocyte protein levels controlling bone turnover. J Bone Miner Res 2017; 32(4): 802-13.
[http://dx.doi.org/10.1002/jbmr.3027] [PMID: 27796050]
[96]
Narayanan SA, Metzger CE, Bloomfield SA, Zawieja DC. Inflammation-induced lymphatic architecture and bone turnover changes are ameliorated by irisin treatment in chronic inflammatory bowel disease. FASEB J 2018; 32(9): 4848-61.
[http://dx.doi.org/10.1096/fj.201800178R] [PMID: 29596023]
[97]
Feng JQ, Ye L, Schiavi S. Do osteocytes contribute to phosphate homeostasis? Curr Opin Nephrol Hypertens 2009; 18(4): 285-91.
[http://dx.doi.org/10.1097/MNH.0b013e32832c224f] [PMID: 19448536]
[98]
van Dijk FS, Zillikens MC, Micha D, et al. PLS3 mutations in X-linked osteoporosis with fractures. N Engl J Med 2013; 369(16): 1529-36.
[http://dx.doi.org/10.1056/NEJMoa1308223] [PMID: 24088043]
[99]
Quarles LD. FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. Am J Physiol Endocrinol Metab 2003; 285(1): E1-9.
[http://dx.doi.org/10.1152/ajpendo.00016.2003] [PMID: 12791601]
[100]
Harris SE, MacDougall M, Horn D, et al. Meox2Cre-mediated disruption of CSF-1 leads to osteopetrosis and osteocyte defects. Bone 2012; 50(1): 42-53.
[http://dx.doi.org/10.1016/j.bone.2011.09.038] [PMID: 21958845]
[101]
Andrukhova O, Zeitz U, Goetz R, Mohammadi M, Lanske B, Erben RG. FGF23 acts directly on renal proximal tubules to induce phosphaturia through activation of the ERK1/2-SGK1 signaling pathway. Bone 2012; 51(3): 621-8.
[http://dx.doi.org/10.1016/j.bone.2012.05.015] [PMID: 22647968]
[102]
Sitara D, Razzaque MS, Hesse M, et al. Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice. Matrix Biol 2004; 23(7): 421-32.
[http://dx.doi.org/10.1016/j.matbio.2004.09.007] [PMID: 15579309]
[103]
Plotkin LI, Bellido T. From inside your bones: Osteocytic signaling pathways as therapeutic targets for bone fragility. Nat Rev Endocrinol 2016; 12(10): 593-605.
[http://dx.doi.org/10.1038/nrendo.2016.71] [PMID: 27230951]
[104]
Kotake S, Udagawa N, Takahashi N, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 1999; 103(9): 1345-52.
[http://dx.doi.org/10.1172/JCI5703] [PMID: 10225978]
[105]
Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res 2001; 16(9): 1575-82.
[http://dx.doi.org/10.1359/jbmr.2001.16.9.1575] [PMID: 11547826]
[106]
Frost HM. The mechanostat: a proposed pathogenic mechanism of osteoporoses and the bone mass effects of mechanical and nonmechanical agents. Bone Miner 1987; 2(2): 73-85.
[PMID: 3333019]
[107]
Knothe Tate ML, Adamson JR, Tami AE, Bauer TW. The osteocyte. Int J Biochem Cell Biol 2004; 36(1): 1-8.
[http://dx.doi.org/10.1016/S1357-2725(03)00241-3] [PMID: 14592527]
[108]
Chao H, Qing-Hua Q. Bone remodeling and biological effects of mechanical stimulus. AIMS Bioeng 2020; 7(1): 12-28.
[http://dx.doi.org/10.3934/bioeng.2020002]
[109]
Wein MN. Parathyroid Hormone Signaling in Osteocytes. JBMR Plus 2017; 2(1): 22-30.
[http://dx.doi.org/10.1002/jbm4.10021] [PMID: 30283888]
[110]
Bonewald LF, Johnson ML. Osteocytes, mechanosensing and Wnt signaling. Bone 2008; 42(4): 606-15.
[http://dx.doi.org/10.1016/j.bone.2007.12.224] [PMID: 18280232]
[111]
Coxon FP, Taylor A. Vesicular trafficking in osteoclasts. Semin Cell Dev Biol 2008; 19(5): 424-33.
[http://dx.doi.org/10.1016/j.semcdb.2008.08.004] [PMID: 18768162]
[112]
Luxenburg C, Geblinger D, Klein E, et al. The architecture of the adhesive apparatus of cultured osteoclasts: from podosome formation to sealing zone assembly. PLoS One 2007; 2(1): e179.
[http://dx.doi.org/10.1371/journal.pone.0000179] [PMID: 17264882]
[113]
Georgess D, Machuca-Gayet I, Blangy A, Jurdic P. Podosome organization drives osteoclast-mediated bone resorption. Cell Adhes Migr 2014; 8(3): 191-204.
[http://dx.doi.org/10.4161/cam.27840] [PMID: 24714644]
[114]
Sims NA, Martin TJ. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. Bonekey Rep 2014; 3: 481.
[http://dx.doi.org/10.1038/bonekey.2013.215] [PMID: 24466412]
[115]
Sims NA, Martin TJ. Coupling Signals between the osteoclast and osteoblast: How are messages transmitted between these temporary visitors to the bone surface. Front Endocrinol (Lausanne) 2015; 6: 41.
[http://dx.doi.org/10.3389/fendo.2015.00041] [PMID: 25852649]
[116]
Matsuo K. Eph and ephrin interactions in bone. Adv Exp Med Biol 2010; 658: 95-103.
[http://dx.doi.org/10.1007/978-1-4419-1050-9_10] [PMID: 19950019]
[117]
Arvanitis D, Davy A. Eph/ephrin signaling: networks. Genes Dev 2008; 22(4): 416-29.
[118]
Kikutani H, Suzuki K, Kumanogoh A. Immune semaphorins: increasing members and their diverse roles. Adv Immunol 2007; 93: 121-43.
[http://dx.doi.org/10.1016/S0065-2776(06)93003-X] [PMID: 17383540]
[119]
Conrotto P, Valdembri D, Corso S, et al. Sema4D induces angiogenesis through Met recruitment by Plexin B1. Blood 2005; 105(11): 4321-9.
[http://dx.doi.org/10.1182/blood-2004-07-2885] [PMID: 15632204]
[120]
Negishi-Koga T, Shinohara M, Komatsu N, et al. Suppression of bone formation by osteoclastic expression of semaphorin 4D. Nat Med 2011; 17(11): 1473-80.
[http://dx.doi.org/10.1038/nm.2489] [PMID: 22019888]
[121]
Lontos K, Adamik J, Tsagianni A, Galson DL, Chirgwin JM, Suvannasankha A. The Role of Semaphorin 4D in Bone Remodeling and Cancer Metastasis. Front Endocrinol (Lausanne) 2018; 9: 322.
[http://dx.doi.org/10.3389/fendo.2018.00322] [PMID: 29971044]
[122]
Matsuoka K, Kohara Y, Naoe Y, et al. WAIF1 Is a Cell-Surface CTHRC1 Binding Protein Coupling Bone Resorption and Formation. J Bone Miner Res 2018; 33(8): 1500-12.
[http://dx.doi.org/10.1002/jbmr.3436] [PMID: 29624737]
[123]
Ikeda K, Takeshita S. Factors and mechanisms involved in the coupling from bone resorption to formation: how osteoclasts talk to osteoblasts. J Bone Metab 2014; 21(3): 163-7.
[http://dx.doi.org/10.11005/jbm.2014.21.3.163] [PMID: 25247154]
[124]
Matsuoka K, Park KA, Ito M, Ikeda K, Takeshita S. Osteoclast-derived complement component 3a stimulates osteoblast differentiation. J Bone Miner Res 2014; 29(7): 1522-30.
[http://dx.doi.org/10.1002/jbmr.2187] [PMID: 24470120]
[125]
Glimcher MJ, Muir H. Recent studies of the mineral phase in bone and its possible linkage to the organic matrix by protein-bound phosphate bonds. Philos Trans R Soc Lond B Biol Sci 1984; 304(1121): 479-508.
[http://dx.doi.org/10.1098/rstb.1984.0041] [PMID: 6142489]
[126]
Blair HC, Larrouture QC, Li Y, et al. Osteoblast Differentiation and Bone Matrix Formation In Vivo and In Vitro. Tissue Eng Part B Rev 2017; 23(3): 268-80.
[http://dx.doi.org/10.1089/ten.teb.2016.0454] [PMID: 27846781]
[127]
Birkhäuser M. Treatment of pain in estrogen deficiency. Arch Gynecol Obstet 1996; 259(Suppl. 1): S74-9.
[PMID: 9133284]
[128]
Hess RA, Bunick D, Lee KH, et al. A role for oestrogens in the male reproductive system. Nature 1997; 390(6659): 509-12.
[http://dx.doi.org/10.1038/37352] [PMID: 9393999]
[129]
Sasano H, Uzuki M, Sawai T, et al. Aromatase in human bone tissue. J Bone Miner Res 1997; 12(9): 1416-23.
[http://dx.doi.org/10.1359/jbmr.1997.12.9.1416] [PMID: 9286757]
[130]
Cenci S, Weitzmann MN, Roggia C, et al. Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J Clin Invest 2000; 106(10): 1229-37.
[http://dx.doi.org/10.1172/JCI11066] [PMID: 11086024]
[131]
Martin-Millan M, Almeida M, Ambrogini E, et al. The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone. Mol Endocrinol 2010; 24(2): 323-34.
[http://dx.doi.org/10.1210/me.2009-0354] [PMID: 20053716]
[132]
Srivastava S, Toraldo MN, Weitzmann S, Cenci FP, Ross R. Pacifici Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-kB ligand (RANKL)-induced JNK activation. J Biol Chem 2001; 276: 8836-40.
[http://dx.doi.org/10.1074/jbc.M010764200] [PMID: 11121427]
[133]
Bord S, Ireland DC, Beavan SR, Compston JE. The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts. Bone 2003; 32(2): 136-41.
[http://dx.doi.org/10.1016/S8756-3282(02)00953-5] [PMID: 12633785]
[134]
Nelson ER, DuSell CD, Wang X, et al. The oxysterol, 27-hydroxycholesterol, links cholesterol metabolism to bone homeostasis through its actions on the estrogen and liver X receptors. Endocrinology 2011; 152(12): 4691-705.
[http://dx.doi.org/10.1210/en.2011-1298] [PMID: 21933863]
[135]
Kousteni S, Han L, Chen JR, et al. Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids. J Clin Invest 2003; 111(11): 1651-64.
[http://dx.doi.org/10.1172/JCI200317261] [PMID: 12782668]
[136]
Piri F, Khosravi A, Moayeri A, Moradipour A, Derakhshan S. The Effects of Dietary Supplements of Calcium, Vitamin D and Estrogen Hormone on Serum Levels of OPG and RANKL Cytokines and their Relationship with Increased Bone Density in Rats. J Clin Diagn Res 2016; 10(9): AF01-4.
[http://dx.doi.org/10.7860/JCDR/2016/18648.8433] [PMID: 27790417]
[137]
Chen H, Senda T, Emura S, Kubo K. An Update on the Structure of the Parathyroid Gland. The open Anatomy Journal 2013; 5: 1-9.
[138]
Kumar R, Thompson JR. The regulation of parathyroid hormone secretion and synthesis. J Am Soc Nephrol 2011; 22(2): 216-24.
[http://dx.doi.org/10.1681/ASN.2010020186] [PMID: 21164021]
[139]
Silva BC, Costa AG, Cusano NE, Kousteni S, Bilezikian JP. Catabolic and anabolic actions of parathyroid hormone on the skeleton. J Endocrinol Invest 2011; 34(10): 801-10.
[PMID: 21946081]
[140]
Datta NS, Abou-Samra AB. PTH and PTHrP signaling in osteoblasts. Cell Signal 2009; 21(8): 1245-54.
[http://dx.doi.org/10.1016/j.cellsig.2009.02.012] [PMID: 19249350]
[141]
Kulkarni NH, Halladay DL, Miles RR, et al. Effects of parathyroid hormone on Wnt signaling pathway in bone. J Cell Biochem 2005; 95(6): 1178-90.
[http://dx.doi.org/10.1002/jcb.20506] [PMID: 15962290]
[142]
Prisby R, Guignandon A, Vanden-Bossche A, et al. Intermittent PTH(1-84) is osteoanabolic but not osteoangiogenic and relocates bone marrow blood vessels closer to bone-forming sites. J Bone Miner Res 2011; 26(11): 2583-96.
[http://dx.doi.org/10.1002/jbmr.459] [PMID: 21713994]
[143]
Yu B, Zhao X, Yang C, et al. Parathyroid hormone induces differentiation of mesenchymal stromal/stem cells by enhancing bone morphogenetic protein signaling. J Bone Miner Res 2012; 27(9): 2001-14.
[http://dx.doi.org/10.1002/jbmr.1663] [PMID: 22589223]
[144]
Crane JL, Cao X. Bone marrow mesenchymal stem cells and TGF-β signaling in bone remodeling. J Clin Invest 2014; 124(2): 466-72.
[http://dx.doi.org/10.1172/JCI70050] [PMID: 24487640]
[145]
Lee AW, Cho SS. Association between phosphorus intake and bone health in the NHANES population. Nutr J 2015; 14: 28.
[http://dx.doi.org/10.1186/s12937-015-0017-0] [PMID: 25856461]
[146]
Li X, Qin L, Bergenstock M, Bevelock LM, Novack DV, Partridge NC. Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts. J Biol Chem 2007; 282(45): 33098-106.
[http://dx.doi.org/10.1074/jbc.M611781200] [PMID: 17690108]
[147]
Sunyecz JA. The use of calcium and vitamin D in the management of osteoporosis. Ther Clin Risk Manag 2008; 4(4): 827-36.
[http://dx.doi.org/10.2147/TCRM.S3552] [PMID: 19209265]
[148]
Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992; 327(23): 1637-42.
[http://dx.doi.org/10.1056/NEJM199212033272305] [PMID: 1331788]
[149]
Veldurthy V, Wei R, Oz L, Dhawan P, Jeon YH, Christakos S. Vitamin D, calcium homeostasis and aging. Bone Res 2016; 4: 16041.
[http://dx.doi.org/10.1038/boneres.2016.41] [PMID: 27790378]
[150]
Lieben L, Benn BS, Ajibade D, et al. Trpv6 mediates intestinal calcium absorption during calcium restriction and contributes to bone homeostasis. Bone 2010; 47(2): 301-8.
[http://dx.doi.org/10.1016/j.bone.2010.04.595] [PMID: 20399919]
[151]
Cui M, Li Q, Johnson R, Fleet JC. Villin promoter-mediated transgenic expression of transient receptor potential cation channel, subfamily V, member 6 (TRPV6) increases intestinal calcium absorption in wild-type and vitamin D receptor knockout mice. J Bone Miner Res 2012; 27(10): 2097-107.
[http://dx.doi.org/10.1002/jbmr.1662] [PMID: 22589201]
[152]
Pansu D, Bellaton C, Roche C, Bronner F. Duodenal and ileal calcium absorption in the rat and effects of vitamin D. Am J Physiol 1983; 244(6): G695-700.
[PMID: 6602556]
[153]
Sözen T, Özışık L, Başaran NC. An overview and management of osteoporosis. Eur J Rheumatol 2017; 4(1): 46-56.
[http://dx.doi.org/10.5152/eurjrheum.2016.048] [PMID: 28293453]
[154]
Crockett JC, Rogers MJ, Coxon FP, Hocking LJ, Helfrich MH. Bone remodelling at a glance. J Cell Sci 2011; 124(Pt 7): 991-8.
[http://dx.doi.org/10.1242/jcs.063032] [PMID: 21402872]
[155]
Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 2005; 115(12): 3318-25.
[http://dx.doi.org/10.1172/JCI27071] [PMID: 16322775]
[156]
Li K, Zhang X, He B, et al. Geraniin promotes osteoblast proliferation and differentiation via the activation of Wnt/β-catenin pathway. Biomed Pharmacother 2018; 99: 319-24.
[http://dx.doi.org/10.1016/j.biopha.2018.01.040] [PMID: 29353207]
[157]
Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature 2000; 408(6809): 239-47.
[http://dx.doi.org/10.1038/35041687] [PMID: 11089981]
[158]
Giorgio M, Trinei M, Migliaccio E, Pelicci PG. Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat Rev Mol Cell Biol 2007; 8(9): 722-8.
[http://dx.doi.org/10.1038/nrm2240] [PMID: 17700625]
[159]
Canalis E. Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity, and deoxyribonucleic acid content in cultured rat calvariae. Endocrinology 1983; 112(3): 931-9.
[http://dx.doi.org/10.1210/endo-112-3-931] [PMID: 6822219]
[160]
Peretz A, Praet JP, Bosson D, Rozenberg S, Bourdoux P. Serum osteocalcin in the assessment of corticosteroid induced osteoporosis. Effect of long and short term corticosteroid treatment. J Rheumatol 1989; 16(3): 363-7.
[PMID: 2786081]
[161]
Galson DL, Roodman GD. Pathobiology of Paget's disease of Bone. J Bone Metab 2014; 21(2): 85-98.
[162]
Singer FR. Paget disease: when to treat and when not to treat. Nat Rev Rheumatol 2009; 5(9): 483-9.
[http://dx.doi.org/10.1038/nrrheum.2009.149] [PMID: 19652650]
[163]
Sabharwal R, Gupta S, Sepolia S, et al. An Insight in to Paget’s Disease of Bone. Niger J Surg 2014; 20(1): 9-15.
[PMID: 24665195]
[164]
Wuyts W, Van Wesenbeeck L, Morales-Piga A, et al. Evaluation of the role of RANK and OPG genes in Paget’s disease of bone. Bone 2001; 28(1): 104-7.
[http://dx.doi.org/10.1016/S8756-3282(00)00411-7] [PMID: 11165949]
[165]
Menaa C, Reddy SV, Kurihara N, et al. Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget’s disease of bone. J Clin Invest 2000; 105(12): 1833-8.
[http://dx.doi.org/10.1172/JCI9133] [PMID: 10862799]
[166]
Sun SG, Lau YS, Itonaga I, Sabokbar A, Athanasou NA. Bone stromal cells in pagetic bone and Paget’s sarcoma express RANKL and support human osteoclast formation. J Pathol 2006; 209(1): 114-20.
[http://dx.doi.org/10.1002/path.1953] [PMID: 16482498]
[167]
Marshall MJ, Evans SF, Sharp CA, Powell DE, McCarthy HS, Davie MWJ. Increased circulating Dickkopf-1 in Paget’s disease of bone. Clin Biochem 2009; 42(10-11): 965-9.
[http://dx.doi.org/10.1016/j.clinbiochem.2009.04.007] [PMID: 19389391]
[168]
Galson DL, Roodman GD. Pathobiology of Paget’s Disease of Bone. J Bone Metab 2014; 21(2): 85-98.
[http://dx.doi.org/10.11005/jbm.2014.21.2.85] [PMID: 25025000]
[169]
Teramachi J, Kurihara N, Windle J, et al. Expression of measles virus nucleocapsid protein (MVNP) gene in osteoclasts induces coupling factors that stimulate bone formation. Poster sessions presented at: ASBMR 2012 Annual Meeting; 2012 October 12-15; Minesota, USA.
[170]
Feng X, McDonald JM. Disorders of Bone Remodeling. Annu Rev Pathol Mech Dis 2011; 6: 121-45.
[http://dx.doi.org/10.1146/annurev-pathol-011110-130203]
[171]
Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res 2018; 6: 15.
[http://dx.doi.org/10.1038/s41413-018-0016-9] [PMID: 29736302]
[172]
Bi H, Chen X, Gao S, et al. Key Triggers of Osteoclast-Related Diseases and Available Strategies for Targeted Therapies: A Review. Front Med (Lausanne) 2017; 4: 234.
[http://dx.doi.org/10.3389/fmed.2017.00234] [PMID: 29326938]
[173]
Okamoto K, Nakashima T, Shinohara M, et al. Osteoimmunology: the conceptual framework unifying the immune and skeletal systems. Physiol Rev 2017; 97(4): 1295-349.
[http://dx.doi.org/10.1152/physrev.00036.2016] [PMID: 28814613]
[174]
Pettit AR, Walsh NC, Manning C, Goldring SR, Gravallese EM. RANKL protein is expressed at the pannus-bone interface at sites of articular bone erosion in rheumatoid arthritis. Rheumatology (Oxford) 2006; 45(9): 1068-76.
[http://dx.doi.org/10.1093/rheumatology/kel045] [PMID: 16490750]
[175]
Stark Z, Savarirayan R. Osteopetrosis. Orphanet J Rare Dis 2009; 4: 5.
[http://dx.doi.org/10.1186/1750-1172-4-5] [PMID: 19232111]
[176]
Hellemans J, Preobrazhenska O, Willaert A, et al. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat Genet 2004; 36(11): 1213-8.
[http://dx.doi.org/10.1038/ng1453] [PMID: 15489854]
[177]
Hellemans J, Debeer P, Wright M, et al. Germline LEMD3 mutations are rare in sporadic patients with isolated melorheostosis. Hum Mutat 2006; 27(3): 290.
[http://dx.doi.org/10.1002/humu.9403] [PMID: 16470551]
[178]
Grzeschik KH, Bornholdt D, Oeffner F, et al. Deficiency of PORCN, a regulator of Wnt signaling, is associated with focal dermal hypoplasia. Nat Genet 2007; 39(7): 833-5.
[http://dx.doi.org/10.1038/ng2052] [PMID: 17546031]
[179]
Wang X, Reid Sutton V, Omar Peraza-Llanes J, et al. Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia. Nat Genet 2007; 39(7): 836-8.
[http://dx.doi.org/10.1038/ng2057] [PMID: 17546030]
[180]
St-Arnaud R, Naja RP. Vitamin D metabolism, cartilage and bone fracture repair. Mol Cell Endocrinol 2011; 347(1-2): 48-54.
[http://dx.doi.org/10.1016/j.mce.2011.05.018] [PMID: 21664253]
[181]
Morris HA, O’Loughlin PD, Anderson PH. Experimental evidence for the effects of calcium and vitamin D on bone: a review. Nutrients 2010; 2(9): 1026-35.
[http://dx.doi.org/10.3390/nu2091026] [PMID: 22254071]
[182]
Geddes JAA, Inderjeeth CA. Evidence for the treatment of osteoporosis with vitamin D in residential care and in the community dwelling elderly. Bio Med Res Int 2013; 2013: 463589.
[http://dx.doi.org/10.1155/2013/463589] [PMID: 24058907]
[183]
Tabatabaei-Malazy O, Salari P, Khashayar P, Larijani B. New horizons in treatment of osteoporosis. Daru 2017; 25(1): 2.
[http://dx.doi.org/10.1186/s40199-017-0167-z] [PMID: 28173850]
[184]
Russell RG. Bisphosphonates: from bench to bedside. Ann N Y Acad Sci 2006; 1068: 367-401.
[http://dx.doi.org/10.1196/annals.1346.041] [PMID: 16831938]
[185]
Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc 2008; 83(9): 1032-45.
[http://dx.doi.org/10.4065/83.9.1032] [PMID: 18775204]
[186]
Dunford JE, Thompson K, Coxon FP, et al. Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 2001; 296(2): 235-42.
[PMID: 11160603]
[187]
Kavanagh KL, Guo K, Dunford JE, et al. The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc Natl Acad Sci USA 2006; 103(20): 7829-34.
[http://dx.doi.org/10.1073/pnas.0601643103] [PMID: 16684881]
[188]
Rodan GA, Reszka AA. Bisphosphonate mechanism of action. Curr Mol Med 2002; 2(6): 571-7.
[http://dx.doi.org/10.2174/1566524023362104] [PMID: 12243249]
[189]
Sato M, Grasser W. Effects of bisphosphonates on isolated rat osteoclasts as examined by reflected light microscopy. J Bone Miner Res 1990; 5(1): 31-40.
[http://dx.doi.org/10.1002/jbmr.5650050107] [PMID: 2106763]
[190]
Alakangas A, Selander K, Mulari M, et al. Alendronate disturbs vesicular trafficking in osteoclasts. Calcif Tissue Int 2002; 70(1): 40-7.
[http://dx.doi.org/10.1007/s002230010047] [PMID: 11907706]
[191]
Mathov I, Plotkin LI, Sgarlata CL, Leoni J, Bellido T. Extracellular signal-regulated kinases and calcium channels are involved in the proliferative effect of bisphosphonates on osteoblastic cells in vitro. J Bone Miner Res 2001; 16(11): 2050-6.
[http://dx.doi.org/10.1359/jbmr.2001.16.11.2050] [PMID: 11697801]
[192]
Hanley DA, Adachi JD, Bell A, Brown V. Denosumab: mechanism of action and clinical outcomes. Int J Clin Pract 2012; 66(12): 1139-46.
[http://dx.doi.org/10.1111/ijcp.12022] [PMID: 22967310]
[193]
Reginster JY, Neuprez A, Dardenne N, Beaudart C, Emonts P, Bruyere O. Efficacy and safety of currently marketed anti-osteoporosis medications. Best Pract Res Clin Endocrinol Metab 2014; 28(6): 809-34.
[http://dx.doi.org/10.1016/j.beem.2014.09.003] [PMID: 25432354]
[194]
Suzuki T, Nakamura Y, Kato H. Changes of bone-related minerals during denosumab administration in post-menopausal osteoporotic patients. Nutrients 2017; 9(8): e871.
[http://dx.doi.org/10.3390/nu9080871] [PMID: 28805705]
[195]
Cheng ML, Fong L. Effects of RANKL-Targeted Therapy in Immunity and Cancer. Front Oncol 2014; 3: 329.
[http://dx.doi.org/10.3389/fonc.2013.00329] [PMID: 24432249]
[196]
Lewiecki EM. Safety and tolerability of denosumab for the treatment of postmenopausal osteoporosis. Drug Healthc Patient Saf 2011; 3: 79-91.
[http://dx.doi.org/10.2147/DHPS.S7727] [PMID: 22279412]
[197]
McClung MR, Lewiecki EM, Cohen SB, et al. AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006; 354(8): 821-31.
[http://dx.doi.org/10.1056/NEJMoa044459] [PMID: 16495394]
[198]
McClung MR. Denosumab for the treatment of osteoporosis. Osteoporos Sarcopenia 2017; 3(1): 8-17.
[http://dx.doi.org/10.1016/j.afos.2017.01.002]
[199]
An KC. Selective Estrogen Receptor Modulators. Asian Spine J 2016; 10(4): 787-91.
[http://dx.doi.org/10.4184/asj.2016.10.4.787] [PMID: 27559463]
[200]
Nilsson S, Koehler KF. Oestrogen receptors and selective oestrogen receptor modulators: molecular and cellular pharmacology. Basic Clin Pharmacol Toxicol 2005; 96(1): 15-25.
[http://dx.doi.org/10.1111/j.1742-7843.2005.pto960103.x] [PMID: 15667591]
[201]
Gennari L, Merlotti D, Valleggi F, Martini G, Nuti R. Selective estrogen receptor modulators for postmenopausal osteoporosis: current state of development. Drugs Aging 2007; 24(5): 361-79.
[http://dx.doi.org/10.2165/00002512-200724050-00002] [PMID: 17503894]
[202]
Gennari L, Merlotti D, De Paola V, Martini G, Nuti R. Bazedoxifene for the prevention of postmenopausal osteoporosis. Ther Clin Risk Manag 2008; 4(6): 1229-42.
[http://dx.doi.org/10.2147/TCRM.S3476] [PMID: 19337430]
[203]
Hu R, Hilakivi-Clarke L, Clarke R. Molecular mechanisms of tamoxifen-associated endometrial cancer (Review). Oncol Lett 2015; 9(4): 1495-501.
[http://dx.doi.org/10.3892/ol.2015.2962] [PMID: 25788989]
[204]
Goldstein SR, Neven P, Cummings S, et al. Postmenopausal Evaluation and Risk Reduction With Lasofoxifene (PEARL) trial: 5-year gynecological outcomes. Menopause 2011; 18(1): 17-22.
[http://dx.doi.org/10.1097/gme.0b013e3181e84bb4] [PMID: 20689465]
[205]
Kulak Júnior J, Kulak CA, Taylor HS. SERMs in the prevention and treatment of postmenopausal osteoporosis: an update. Arq Bras Endocrinol Metabol 2010; 54(2): 200-5.
[http://dx.doi.org/10.1590/S0004-27302010000200016] [PMID: 20485909]
[206]
Lello S, Capozzi A, Scambia G. The Tissue-Selective Estrogen Complex (Bazedoxifene/Conjugated Estrogens) for the Treatment of Menopause. Int J Endocrinol 2017; 2017: 5064725.
[http://dx.doi.org/10.1155/2017/5064725] [PMID: 29358948]
[207]
Tella SH, Gallagher JC. Prevention and treatment of postmenopausal osteoporosis. J Steroid Biochem Mol Biol 2014; 142: 155-70.
[http://dx.doi.org/10.1016/j.jsbmb.2013.09.008] [PMID: 24176761]
[208]
Muñoz-Torres M, Alonso G, Raya MP. Calcitonin therapy in osteoporosis. Treat Endocrinol 2004; 3(2): 117-32.
[http://dx.doi.org/10.2165/00024677-200403020-00006] [PMID: 15743107]
[209]
Pavone V, Testa G, Giardina SMC, Vescio A, Restivo DA, Sessa G. Pharmacological therapy of osteoporosis: A systematic current review of literature. Front Pharmacol 2017; 8: 803.
[http://dx.doi.org/10.3389/fphar.2017.00803] [PMID: 29163183]
[210]
Wells G, Chernoff J, Gilligan JP, Krause DS. Does salmon calcitonin cause cancer? A review and meta-analysis. Osteoporos Int 2016; 27(1): 13-9.
[http://dx.doi.org/10.1007/s00198-015-3339-z] [PMID: 26438308]
[211]
McCudden CR, Hains MD, Kimple RJ, Siderovski DP, Willard FS. G-protein signaling: back to the future. Cell Mol Life Sci 2005; 62(5): 551-77.
[http://dx.doi.org/10.1007/s00018-004-4462-3] [PMID: 15747061]
[212]
Frolik CA, Black EC, Cain RL, et al. Anabolic and catabolic bone effects of human parathyroid hormone (1-34) are predicted by duration of hormone exposure. Bone 2003; 33(3): 372-9.
[http://dx.doi.org/10.1016/S8756-3282(03)00202-3] [PMID: 13678779]
[213]
Denise Jahn GR, Appelt J, Märdian S, Tsitsilonis S, Keller J. Anabolic therapies in osteoporosis and bone regeneration. Int J Mol Sci 2019; 83: 1-17.
[214]
Leder BZ, O’Dea LS, Zanchetta JR, et al. Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 2015; 100(2): 697-706.
[http://dx.doi.org/10.1210/jc.2014-3718] [PMID: 25393645]
[215]
Hodsman AB, Bauer DC, Dempster DW, et al. Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocr Rev 2005; 26(5): 688-703.
[http://dx.doi.org/10.1210/er.2004-0006] [PMID: 15769903]
[216]
Haas AV, LeBoff MS. Osteoanabolic Agents for Osteoporosis. J Endocr Soc 2018; 2(8): 922-32.
[http://dx.doi.org/10.1210/js.2018-00118] [PMID: 30087947]
[217]
Meunier PJ. Anabolic agents for treating postmenopausal osteoporosis. Joint Bone Spine 2001; 68(6): 576-81.
[http://dx.doi.org/10.1016/S1297-319X(01)00329-3] [PMID: 11809001]
[218]
Shane E, Burr D, Abrahamsen B, et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2014; 29(1): 1-23.
[http://dx.doi.org/10.1002/jbmr.1998] [PMID: 23712442]
[219]
Crandall CJ, Newberry SJ, Diamant A. Comparative effectiveness of pharmacologic treatments to prevent fractures: An updated systematic review. Ann Intern Med 2014; 161: 711-23.
[220]
Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 2016; 375(16): 1532-43.
[http://dx.doi.org/10.1056/NEJMoa1607948] [PMID: 27641143]
[221]
Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ. Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One 2011; 6(10): e25900.
[http://dx.doi.org/10.1371/journal.pone.0025900] [PMID: 21991382]
[222]
Recker RR, Benson CT, Matsumoto T, et al. A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density. J Bone Miner Res 2015; 30(2): 216-24.
[http://dx.doi.org/10.1002/jbmr.2351] [PMID: 25196993]
[223]
Murphy MG, Cerchio K, Stoch SA, Gottesdiener K, Wu M, Recker R. L-000845704 Study Group. Effect of L-000845704, an alphaVbeta3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab 2005; 90(4): 2022-8.
[http://dx.doi.org/10.1210/jc.2004-2126] [PMID: 15687321]
[224]
Lin TH, Yang RS, Tu HJ, et al. Inhibition of osteoporosis by the αvβ3 integrin antagonist of rhodostomin variants. Eur J Pharmacol 2017; 804: 94-101.
[http://dx.doi.org/10.1016/j.ejphar.2017.03.019] [PMID: 28315346]
[225]
Carron CP, Meyer DM, Engleman VW, et al. Peptidomimetic antagonists of alphavbeta3 inhibit bone resorption by inhibiting osteoclast bone resorptive activity, not osteoclast adhesion to bone. J Endocrinol 2000; 165(3): 587-98.
[http://dx.doi.org/10.1677/joe.0.1650587] [PMID: 10828842]
[226]
Balkan W, Martinez AF, Fernandez I, Rodriguez MA, Pang M, Troen BR. Identification of NFAT binding sites that mediate stimulation of cathepsin K promoter activity by RANK ligand. Gene 2009; 446(2): 90-8.
[http://dx.doi.org/10.1016/j.gene.2009.06.013] [PMID: 19563866]
[227]
Fuller K, Lawrence KM, Ross JL, et al. Cathepsin K inhibitors prevent matrix-derived growth factor degradation by human osteoclasts. Bone 2008; 42(1): 200-11.
[http://dx.doi.org/10.1016/j.bone.2007.09.044] [PMID: 17962093]
[228]
Pérez-Castrillon JL, Pinacho F, Mambrilla MR, Dueñas Laita A. Odanacatib: a possible new therapeutic option for the treatment of osteoporosis. Int J Clin Rheumatol 2012; 7(4): 369-76.
[http://dx.doi.org/10.2217/ijr.12.33]
[229]
Stoch SA, Wagner JA. Cathepsin K inhibitors: a novel target for osteoporosis therapy. Clin Pharmacol Ther 2008; 83(1): 172-6.
[http://dx.doi.org/10.1038/sj.clpt.6100450] [PMID: 18073778]
[230]
Nagase S, Ohyama M, Hashimoto Y, Small M, Kuwayama T, Deacon S. Pharmacodynamic effects on biochemical markers of bone turnover and pharmacokinetics of the cathepsin K inhibitor, ONO-5334, in an ascending multiple-dose, phase 1 study. J Clin Pharmacol 2012; 52(3): 306-18.
[http://dx.doi.org/10.1177/0091270011399080] [PMID: 21719717]
[231]
Eastell R, Nagase S, Ohyama M, et al. Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: the OCEAN study. J Bone Miner Res 2011; 26(6): 1303-12.
[http://dx.doi.org/10.1002/jbmr.341] [PMID: 21312264]
[232]
Boyce B, Xing L. Src inhibitors in the treatment of metastatic bone disease: rationale and clinical data. Clin Investig (Lond) 2011; 1(12): 1695-706.
[http://dx.doi.org/10.4155/cli.11.150] [PMID: 22384312]
[233]
Hannon RA, Clack G, Rimmer M, et al. Effects of the Src kinase inhibitor saracatinib (AZD0530) on bone turnover in healthy men: a randomized, double-blind, placebo-controlled, multiple-ascending-dose phase I trial. J Bone Miner Res 2010; 25(3): 463-71.
[http://dx.doi.org/10.1359/jbmr.090830] [PMID: 19775203]
[234]
Lange PF, Wartosch L, Jentsch TJ, Fuhrmann JC. ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function. Nature 2006; 440(7081): 220-3.
[http://dx.doi.org/10.1038/nature04535] [PMID: 16525474]
[235]
Chen M, Qiao H, Su Z, Li H, Ping Q, Zong L. Emerging therapeutic targets for osteoporosis treatment. Expert Opin Ther Targets 2014; 18(7): 817-31.
[http://dx.doi.org/10.1517/14728222.2014.912632] [PMID: 24766518]
[236]
Péter S, Eggersdorfer M, van Asselt D, et al. Selected nutrients and their implications for health and disease across the lifespan: a roadmap. Nutrients 2014; 6(12): 6076-94.
[http://dx.doi.org/10.3390/nu6126076] [PMID: 25533014]
[237]
Kruger MC, Wolber FM. Osteoporosis: modern paradigms for last century’s bones. Nutrients 2016; 8(6): 1-12.
[http://dx.doi.org/10.3390/nu8060376] [PMID: 27322315]
[238]
Bringhurst FR, Demay MB, Krane SM, Kronenberg HM. Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw Medical Publishing Division;Bone and mineral metabolism in health and disease 2005; pp. 2246-9.

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