Application of Cytokines of the Bone Morphogenetic Protein (BMP) Family in Spinal Fusion - Effects on the Bone, Intervertebral Disc and Mesenchymal Stromal Cells

Author(s): Rahel Deborah May, Daniela Angelika Frauchiger, Christoph Emmanuel Albers, Adel Tekari, Lorin Michael Benneker, Frank Michael Klenke, Willy Hofstetter, Benjamin Gantenbein*

Journal Name: Current Stem Cell Research & Therapy

Volume 14 , Issue 8 , 2019

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Abstract:

Low back pain is a prevalent socio-economic burden and is often associated with damaged or degenerated intervertebral discs (IVDs). When conservative therapy fails, removal of the IVD (discectomy), followed by intersomatic spinal fusion, is currently the standard practice in clinics. The remaining space is filled with an intersomatic device (cage) and with bone substitutes to achieve disc height compensation and bone fusion. As a complication, in up to 30% of cases, spinal non-fusions result in a painful pseudoarthrosis. Bone morphogenetic proteins (BMPs) have been clinically applied with varied outcomes. Several members of the BMP family, such as BMP2, BMP4, BMP6, BMP7, and BMP9, are known to induce osteogenesis. Questions remain on why hyper-physiological doses of BMPs do not show beneficial effects in certain patients. In this respect, BMP antagonists secreted by mesenchymal cells, which might interfere with or block the action of BMPs, have drawn research attention as possible targets for the enhancement of spinal fusion or the prevention of non-unions. Examples of these antagonists are noggin, gremlin1 and 2, chordin, follistatin, BMP3, and twisted gastrulation. In this review, we discuss current evidence of the osteogenic effects of several members of the BMP family on osteoblasts, IVD cells, and mesenchymal stromal cells. We consider in vitro and in vivo studies performed in human, mouse, rat, and rabbit related to BMP and BMP antagonists in the last two decades. We give insights into the effects that BMP have on the ossification of the spine. Furthermore, the benefits, pitfalls, and possible safety concerns using these cytokines for the improvement of spinal fusion are discussed.

Keywords: Spinal fusion, intervertebral discs, mesenchymal stromal cells, osteogenesis, bone morphogenetic proteins, antagonists of bone morphogenetic proteins.

[1]
Rubin DI. Epidemiology and risk factors for spine pain. Neurol Clin 2007; 25(2): 353-71.
[http://dx.doi.org/10.1016/j.ncl.2007.01.004] [PMID: 17445733]
[2]
Hoy D, March L, Brooks P, et al. The global burden of low back pain: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis 2014; 73(6): 968-74.
[http://dx.doi.org/10.1136/annrheumdis-2013-204428] [PMID: 24665116]
[3]
Knezevic NN, Mandalia S, Raasch J, Knezevic I, Candido KD. Treatment of chronic low back pain - new approaches on the horizon. J Pain Res 2017; 10: 1111-23.
[http://dx.doi.org/10.2147/JPR.S132769] [PMID: 28546769]
[4]
Vaz K, Verma K, Protopsaltis T, Schwab F, Lonner B, Errico T. Bone grafting options for lumbar spine surgery: A review examining clinical efficacy and complications. SAS J 2010; 4(3): 75-86.
[http://dx.doi.org/10.1016/j.esas.2010.01.004] [PMID: 25802654]
[5]
Bodalia PN, Balaji V, Kaila R, Wilson L. Effectiveness and safety of recombinant human bone morphogenetic protein-2 for adults with lumbar spine pseudarthrosis following spinal fusion surgery: A systematic review. Bone Joint Res 2016; 5(4): 145-52.
[http://dx.doi.org/10.1302/2046-3758.54.2000418] [PMID: 27121215]
[6]
Brown SJ, Turner SA, Balain BS, Davidson NT, Roberts S. Is osteogenic differentiation of human nucleus pulposus cells a possibility for biological spinal fusion? Cartilage 2018; •••1947603518754628
[http://dx.doi.org/10.1177/1947603518754628] [PMID: 29361851]
[7]
Berjano P, Langella F, Damilano M, et al. Fusion rate following extreme lateral lumbar interbody fusion. Eur Spine J 2015; 24(Suppl. 3): 369-71.
[http://dx.doi.org/10.1007/s00586-015-3929-7] [PMID: 25893332]
[8]
Chun DS, Baker KC, Hsu WK. Lumbar pseudarthrosis: A review of current diagnosis and treatment. Neurosurg Focus 2015; 39(4)E10
[http://dx.doi.org/10.3171/2015.7.FOCUS15292] [PMID: 26424334]
[9]
DePalma AF, Rothman RH. The nature of pseudoarthrosis. 1968. Clin Orthop Relat Res 1992; (284): 3-9.
[PMID: 1395309]
[10]
Osterman H, Sund R, Seitsalo S, Keskimäki I. Risk of multiple reoperations after lumbar discectomy: a population-based study. Spine 2003; 28(6): 621-7.
[http://dx.doi.org/10.1097/01.BRS.0000049908.15854.ED] [PMID: 12642772]
[11]
Walsh DW, Godson C, Brazil DP, Martin F. Extracellular BMP-antagonist regulation in development and disease: Tied up in knots. Trends Cell Biol 2010; 20(5): 244-56.
[http://dx.doi.org/10.1016/j.tcb.2010.01.008] [PMID: 20188563]
[12]
Wu M, Chen G, Li Y-P. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res 2016; 4: 16009.
[http://dx.doi.org/10.1038/boneres.2016.9] [PMID: 27563484]
[13]
Nolan K, Thompson TB. The DAN family: Modulators of TGF-β signaling and beyond. Protein Sci 2014; 23(8): 999-1012.
[http://dx.doi.org/10.1002/pro.2485] [PMID: 24810382]
[14]
Brazil DP, Church RH, Surae S, Godson C, Martin F. BMP signalling: agony and antagony in the family. Trends Cell Biol 2015; 25(5): 249-64.
[http://dx.doi.org/10.1016/j.tcb.2014.12.004] [PMID: 25592806]
[15]
Worthley DL, Churchill M, Compton JT, et al. Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. Cell 2015; 160(1-2): 269-84.
[http://dx.doi.org/10.1016/j.cell.2014.11.042] [PMID: 25594183]
[16]
Vaibhav B, Nilesh P, Vikram S, Anshul C. Bone morphogenic protein and its application in trauma cases: A current concept update. Injury 2007; 38(11): 1227-35.
[http://dx.doi.org/10.1016/j.injury.2006.12.012] [PMID: 17307180]
[17]
Axelrad TW, Einhorn TA. Bone morphogenetic proteins in orthopaedic surgery. Cytokine Growth Factor Rev 2009; 20(5-6): 481-8.
[http://dx.doi.org/10.1016/j.cytogfr.2009.10.003] [PMID: 19892584]
[18]
Argintar E, Edwards S, Delahay J. Bone morphogenetic proteins in orthopaedic trauma surgery. Injury 2011; 42(8): 730-4.
[http://dx.doi.org/10.1016/j.injury.2010.11.016] [PMID: 21145058]
[19]
Burkus JK, Gornet MF, Dickman CA, Zdeblick TA. Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages. J Spinal Disord Tech 2002; 15(5): 337-49.
[http://dx.doi.org/10.1097/00024720-200210000-00001] [PMID: 12394656]
[20]
Cheng H, Jiang W, Phillips FM, et al. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am 2003; 85(8): 1544-52.
[http://dx.doi.org/10.2106/00004623-200308000-00017] [PMID: 12925636]
[21]
McClellan JW, Mulconrey DS, Forbes RJ, Fullmer N. Vertebral bone resorption after transforaminal lumbar interbody fusion with bone morphogenetic protein (rhBMP-2). J Spinal Disord Tech 2006; 19(7): 483-6.
[http://dx.doi.org/10.1097/01.bsd.0000211231.83716.4b] [PMID: 17021411]
[22]
Buttermann GR. Prospective nonrandomized comparison of an allograft with bone morphogenic protein versus an iliac-crest autograft in anterior cervical discectomy and fusion. Spine J 2008; 8(3): 426-35.
[http://dx.doi.org/10.1016/j.spinee.2006.12.006] [PMID: 17977799]
[23]
Garrison KR, Shemilt I, Donell S, et al. Bone morphogenetic protein (BMP) for fracture healing in adults. Cochrane Database Syst Rev 2010; (6): CD006950
[http://dx.doi.org/10.1002/14651858.CD006950.pub2] [PMID: 20556771]
[24]
Poynton AR, Lane JM. Safety profile for the clinical use of bone morphogenetic proteins in the spine. Spine 2002; 27(16)(Suppl. 1): S40-8.
[http://dx.doi.org/10.1097/00007632-200208151-00010] [PMID: 12205419]
[25]
Govender S, Csimma C, Genant HK, et al. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am 2002; 84(12): 2123-34.
[http://dx.doi.org/10.2106/00004623-200212000-00001] [PMID: 12473698]
[26]
Boden SD, Labropoulos PA, Ragsdale BD, Gullino PM, Gerber LH. Retinyl acetate-induced arthritis in C3H-A(vy) mice. Arthritis Rheum 1989; 32(5): 625-33.
[http://dx.doi.org/10.1002/anr.1780320517] [PMID: 2719733]
[27]
Song K, Krause C, Shi S, et al. Identification of a key residue mediating bone morphogenetic protein (BMP)-6 resistance to noggin inhibition allows for engineered BMPs with superior agonist activity. J Biol Chem 2010; 285(16): 12169-80.
[http://dx.doi.org/10.1074/jbc.M109.087197] [PMID: 20048150]
[28]
Cahill KS, Chi JH, Day A, Claus EB. Prevalence, complications, and hospital charges associated with use of bone-morphogenetic proteins in spinal fusion procedures. JAMA 2009; 302(1): 58-66.
[http://dx.doi.org/10.1001/jama.2009.956] [PMID: 19567440]
[29]
Carragee EJ, Hurwitz EL, Weiner BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J 2011; 11(6): 471-91.
[http://dx.doi.org/10.1016/j.spinee.2011.04.023] [PMID: 21729796]
[30]
Simmonds MC, Brown JV, Heirs MK, et al. Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data. Ann Intern Med 2013; 158(12): 877-89.
[http://dx.doi.org/10.7326/0003-4819-158-12-201306180-00005] [PMID: 23778905]
[31]
Lo KW, Ulery BD, Ashe KM, Laurencin CT. Studies of bone morphogenetic protein-based surgical repair. Adv Drug Deliv Rev 2012; 64(12): 1277-91.
[http://dx.doi.org/10.1016/j.addr.2012.03.014] [PMID: 22512928]
[32]
Hruska KA, Guo G, Wozniak M, et al. Osteogenic protein-1 prevents renal fibrogenesis associated with ureteral obstruction. Am J Physiol Renal Physiol 2000; 279(1): F130-43.
[http://dx.doi.org/10.1152/ajprenal.2000.279.1.F130] [PMID: 10894795]
[33]
Kloen P, Lauzier D, Hamdy RC. Co-expression of BMPs and BMP-inhibitors in human fractures and non-unions. Bone 2012; 51(1): 59-68.
[http://dx.doi.org/10.1016/j.bone.2012.03.032] [PMID: 22521262]
[34]
Chan SC, Tekari A, Benneker LM, Heini PF, Gantenbein B. Osteogenic differentiation of bone marrow stromal cells is hindered by the presence of intervertebral disc cells. Arthritis Res Ther 2015; 18: 29.
[http://dx.doi.org/10.1186/s13075-015-0900-2] [PMID: 26809343]
[35]
May RD, Frauchiger DA, Albers CE, Benneker LM, Kohl S, Gantenbein B. Inhibitory Effects of Human Primary Intervertebral Disc Cells on Human Primary Osteoblasts in a Co-Culture System. Int J Mol Sci 2018; 19(4): 19.
[http://dx.doi.org/10.3390/ijms19041195] [PMID: 29652862]
[36]
Salgado AJ, Coutinho OP, Reis RL. Bone tissue engineering: State of the art and future trends. Macromol Biosci 2004; 4(8): 743-65.
[http://dx.doi.org/10.1002/mabi.200400026] [PMID: 15468269]
[37]
Urist MR. Bone: Formation by autoinduction. Science 1965; 150(3698): 893-9.
[http://dx.doi.org/10.1126/science.150.3698.893] [PMID: 5319761]
[38]
Shehadi JA, Elzein SM. Review of commercially available demineralized bone matrix products for spinal fusions: A selection paradigm. Surg Neurol Int 2017; 8: 203.
[http://dx.doi.org/10.4103/sni.sni_155_17] [PMID: 28904830]
[39]
Gamradt SC, Lieberman JR. Bone graft for revision hip arthroplasty: biology and future applications. Clin Orthop Relat Res 2003; (417): 183-94.
[PMID: 14646716]
[40]
Grgurevic L, Pecina M, Vukicevic S, Marshall R, Marshall R. Urist and the discovery of bone morphogenetic proteins. Int Orthop 2017; 41(5): 1065-9.
[http://dx.doi.org/10.1007/s00264-017-3402-9] [PMID: 28188395]
[41]
Wozney JM, Rosen V, Celeste AJ, et al. Novel regulators of bone formation: molecular clones and activities. Science 1988; 242(4885): 1528-34.
[http://dx.doi.org/10.1126/science.3201241] [PMID: 3201241]
[42]
Johnson EE, Urist MR, Finerman GA. Bone morphogenetic protein augmentation grafting of resistant femoral nonunions. A preliminary report. Clin Orthop Relat Res 1988; (230): 257-65.
[PMID: 3284678]
[43]
Kobayashi T, Lyons KM, McMahon AP, Kronenberg HM. BMP signaling stimulates cellular differentiation at multiple steps during cartilage development. Proc Natl Acad Sci USA 2005; 102(50): 18023-7.
[http://dx.doi.org/10.1073/pnas.0503617102] [PMID: 16322106]
[44]
Tsuji K, Bandyopadhyay A, Harfe BD, et al. BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat Genet 2006; 38(12): 1424-9.
[http://dx.doi.org/10.1038/ng1916] [PMID: 17099713]
[45]
Huang Z, Wang D, Ihida-Stansbury K, Jones PL, Martin JF. Defective pulmonary vascular remodeling in Smad8 mutant mice. Hum Mol Genet 2009; 18(15): 2791-801.
[http://dx.doi.org/10.1093/hmg/ddp214] [PMID: 19419974]
[46]
Hemmati-Brivanlou A, Thomsen GH. Ventral mesodermal patterning in Xenopus embryos: expression patterns and activities of BMP-2 and BMP-4. Dev Genet 1995; 17(1): 78-89.
[http://dx.doi.org/10.1002/dvg.1020170109] [PMID: 7554498]
[47]
Zou H, Niswander L. Requirement for BMP signaling in interdigital apoptosis and scale formation. Science 1996; 272(5262): 738-41.
[http://dx.doi.org/10.1126/science.272.5262.738] [PMID: 8614838]
[48]
Winbanks CE, Chen JL, Qian H, et al. The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass. J Cell Biol 2013; 203(2): 345-57.
[http://dx.doi.org/10.1083/jcb.201211134] [PMID: 24145169]
[49]
Torihashi S, Hattori T, Hasegawa H, Kurahashi M, Ogaeri T, Fujimoto T. The expression and crucial roles of BMP signaling in development of smooth muscle progenitor cells in the mouse embryonic gut. Differentiation 2009; 77(3): 277-89.
[http://dx.doi.org/10.1016/j.diff.2008.10.003] [PMID: 19272526]
[50]
Zhang H, Bradley A. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 1996; 122(10): 2977-86.
[PMID: 8898212]
[51]
Esquela AF, Lee SJ. Regulation of metanephric kidney development by growth/differentiation factor 11. Dev Biol 2003; 257(2): 356-70.
[http://dx.doi.org/10.1016/S0012-1606(03)00100-3] [PMID: 12729564]
[52]
Gram J. Eye development. Curr Top Dev Biol 2010; 90: 343-86.
[http://dx.doi.org/10.1016/S0070-2153(10)90010-0] [PMID: 20691855]
[53]
Settle S, Marker P, Gurley K, et al. The BMP family member Gdf7 is required for seminal vesicle growth, branching morphogenesis, and cytodifferentiation. Dev Biol 2001; 234(1): 138-50.
[http://dx.doi.org/10.1006/dbio.2001.0244] [PMID: 11356025]
[54]
Huang H, Song TJ, Li X, et al. BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc Natl Acad Sci USA 2009; 106(31): 12670-5.
[http://dx.doi.org/10.1073/pnas.0906266106] [PMID: 19620713]
[55]
Wang RN, Green J, Wang Z, et al. Bone Morphogenetic Protein (BMP) signaling in development and human diseases. Genes Dis 2014; 1(1): 87-105.
[http://dx.doi.org/10.1016/j.gendis.2014.07.005] [PMID: 25401122]
[56]
Winnier G, Blessing M, Labosky PA, Hogan BL. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 1995; 9(17): 2105-16.
[http://dx.doi.org/10.1101/gad.9.17.2105] [PMID: 7657163]
[57]
Dunn NR, Winnier GE, Hargett LK, Schrick JJ, Fogo AB, Hogan BL. Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol 1997; 188(2): 235-47.
[http://dx.doi.org/10.1006/dbio.1997.8664] [PMID: 9268572]
[58]
Suzuki N, Labosky PA, Furuta Y, et al. Failure of ventral body wall closure in mouse embryos lacking a procollagen C-proteinase encoded by Bmp1, a mammalian gene related to Drosophila tolloid. Development 1996; 122(11): 3587-95.
[PMID: 8951074]
[59]
McPherron AC, Lawler AM, Lee SJ. Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11. Nat Genet 1999; 22(3): 260-4.
[http://dx.doi.org/10.1038/10320] [PMID: 10391213]
[60]
Dudley AT, Lyons KM, Robertson EJ. A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev 1995; 9(22): 2795-807.
[http://dx.doi.org/10.1101/gad.9.22.2795] [PMID: 7590254]
[61]
Luo G, Hofmann C, Bronckers AL, Sohocki M, Bradley A, Karsenty G. BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev 1995; 9(22): 2808-20.
[http://dx.doi.org/10.1101/gad.9.22.2808] [PMID: 7590255]
[62]
Rosen V. BMP and BMP inhibitors in bone. Ann N Y Acad Sci 2006; 1068: 19-25.
[http://dx.doi.org/10.1196/annals.1346.005] [PMID: 16831902]
[63]
Chen G, Deng C, Li YP. TGF-β and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci 2012; 8(2): 272-88.
[http://dx.doi.org/10.7150/ijbs.2929] [PMID: 22298955]
[64]
Zhang R, Oyajobi BO, Harris SE, et al. Wnt/β-catenin signaling activates bone morphogenetic protein 2 expression in osteoblasts. Bone 2013; 52(1): 145-56.
[http://dx.doi.org/10.1016/j.bone.2012.09.029] [PMID: 23032104]
[65]
Canalis E, Economides AN, Gazzerro E. Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev 2003; 24(2): 218-35.
[http://dx.doi.org/10.1210/er.2002-0023] [PMID: 12700180]
[66]
He X, Liu Y, Yuan X, Lu L. Enhanced healing of rat calvarial defects with MSCs loaded on BMP-2 releasing chitosan/alginate/hydroxyapatite scaffolds. PLoS One 2014; 9(8)e104061
[http://dx.doi.org/10.1371/journal.pone.0104061] [PMID: 25084008]
[67]
Miyazono K, Maeda S, Imamura T. BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 2005; 16(3): 251-63.
[http://dx.doi.org/10.1016/j.cytogfr.2005.01.009] [PMID: 15871923]
[68]
Nohe A, Keating E, Underhill TM, Knaus P, Petersen NO. Dynamics and interaction of caveolin-1 isoforms with BMP-receptors. J Cell Sci 2005; 118(Pt 3): 643-50.
[http://dx.doi.org/10.1242/jcs.01402] [PMID: 15657086]
[69]
de Caestecker M. The transforming growth factor-beta superfamily of receptors. Cytokine Growth Factor Rev 2004; 15(1): 1-11.
[http://dx.doi.org/10.1016/j.cytogfr.2003.10.004] [PMID: 14746809]
[70]
Balemans W, Van Hul W. Extracellular regulation of BMP signaling in vertebrates: a cocktail of modulators. Dev Biol 2002; 250(2): 231-50.
[http://dx.doi.org/10.1006/dbio.2002.0779] [PMID: 12376100]
[71]
Ducy P, Starbuck M, Priemel M, et al. A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev 1999; 13(8): 1025-36.
[http://dx.doi.org/10.1101/gad.13.8.1025] [PMID: 10215629]
[72]
Harada H, Tagashira S, Fujiwara M, et al. Cbfa1 isoforms exert functional differences in osteoblast differentiation. J Biol Chem 1999; 274(11): 6972-8.
[http://dx.doi.org/10.1074/jbc.274.11.6972] [PMID: 10066751]
[73]
Lee MH, Kwon TG, Park HS, Wozney JM, Ryoo HM. BMP-2-induced Osterix expression is mediated by Dlx5 but is independent of Runx2. Biochem Biophys Res Commun 2003; 309(3): 689-94.
[http://dx.doi.org/10.1016/j.bbrc.2003.08.058] [PMID: 12963046]
[74]
Pereira RM, Delany AM, Canalis E. Cortisol inhibits the differentiation and apoptosis of osteoblasts in culture. Bone 2001; 28(5): 484-90.
[http://dx.doi.org/10.1016/S8756-3282(01)00422-7] [PMID: 11344047]
[75]
Rider CC, Mulloy B. Bone morphogenetic protein and growth differentiation factor cytokine families and their protein antagonists. Biochem J 2010; 429(1): 1-12.
[http://dx.doi.org/10.1042/BJ20100305] [PMID: 20545624]
[76]
Merino R, Rodriguez-Leon J, Macias D, Gañan Y, Economides AN, Hurle JM. The BMP antagonist Gremlin regulates outgrowth, chondrogenesis and programmed cell death in the developing limb. Development 1999; 126(23): 5515-22.
[PMID: 10556075]
[77]
Dudarić L, Cvek SZ, Cvijanović O, et al. Expression of the BMP-2, -4 and -7 and their antagonists gremlin, chordin, noggin and follistatin during ectopic osteogenesis. Coll Antropol 2013; 37(4): 1291-8.
[PMID: 24611347]
[78]
Church RH, Krishnakumar A, Urbanek A, et al. Gremlin1 preferentially binds to bone morphogenetic protein-2 (BMP-2) and BMP-4 over BMP-7. Biochem J 2015; 466(1): 55-68.
[http://dx.doi.org/10.1042/BJ20140771] [PMID: 25378054]
[79]
Iemura S, Yamamoto TS, Takagi C, et al. Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo. Proc Natl Acad Sci USA 1998; 95(16): 9337-42.
[http://dx.doi.org/10.1073/pnas.95.16.9337] [PMID: 9689081]
[80]
Yeung CY, Gossan N, Lu Y, et al. Gremlin-2 is a BMP antagonist that is regulated by the circadian clock. Sci Rep 2014; 4: 5183.
[http://dx.doi.org/10.1038/srep05183] [PMID: 24897937]
[81]
Wang CL, Xiao F, Wang CD, et al. Gremlin2 Suppression Increases the BMP-2-Induced Osteogenesis of Human Bone Marrow-Derived Mesenchymal Stem Cells Via the BMP-2/Smad/Runx2 Signaling Pathway. J Cell Biochem 2017; 118(2): 286-97.
[http://dx.doi.org/10.1002/jcb.25635] [PMID: 27335248]
[82]
Aoki H, Fujii M, Imamura T, et al. Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction. J Cell Sci 2001; 114(Pt 8): 1483-9.
[PMID: 11282024]
[83]
Schmidl M, Adam N, Surmann-Schmitt C, et al. Twisted gastrulation modulates bone morphogenetic protein-induced collagen II and X expression in chondrocytes in vitro and in vivo. J Biol Chem 2006; 281(42): 31790-800.
[http://dx.doi.org/10.1074/jbc.M603419200] [PMID: 16905550]
[84]
Chang C, Holtzman DA, Chau S, et al. Twisted gastrulation can function as a BMP antagonist. Nature 2001; 410(6827): 483-7.
[http://dx.doi.org/10.1038/35068583] [PMID: 11260717]
[85]
Larraín J, Bachiller D, Lu B, Agius E, Piccolo S, De Robertis EM. BMP-binding modules in chordin: a model for signalling regulation in the extracellular space. Development 2000; 127(4): 821-30.
[PMID: 10648240]
[86]
Thouverey C, Caverzasio J. Sclerostin inhibits osteoblast differentiation without affecting BMP2/SMAD1/5 or Wnt3a/β-catenin signaling but through activation of platelet-derived growth factor receptor signaling in vitro. Bonekey Rep 2015; 4: 757.
[http://dx.doi.org/10.1038/bonekey.2015.126] [PMID: 26587226]
[87]
Song B, Estrada KD, Lyons KM. Smad signaling in skeletal development and regeneration. Cytokine Growth Factor Rev 2009; 20(5-6): 379-88.
[http://dx.doi.org/10.1016/j.cytogfr.2009.10.010] [PMID: 19926329]
[88]
Lamplot JD, Qin J, Nan G, et al. BMP9 signaling in stem cell differentiation and osteogenesis. Am J Stem Cells 2013; 2(1): 1-21.
[PMID: 23671813]
[89]
Rahman MS, Akhtar N, Jamil HM, Banik RS, Asaduzzaman SM. TGF-β/BMP signaling and other molecular events: Regulation of osteoblastogenesis and bone formation. Bone Res 2015; 3: 15005.
[http://dx.doi.org/10.1038/boneres.2015.5] [PMID: 26273537]
[90]
García de Vinuesa A, Abdelilah-Seyfried S, Knaus P, Zwijsen A, Bailly S. BMP signaling in vascular biology and dysfunction. Cytokine Growth Factor Rev 2016; 27: 65-79.
[http://dx.doi.org/10.1016/j.cytogfr.2015.12.005] [PMID: 26823333]
[91]
Pierre A, Pisselet C, Monget P, Monniaux D, Fabre S. Testing the antagonistic effect of follistatin on BMP family members in ovine granulosa cells. Reprod Nutr Dev 2005; 45(4): 419-25.
[http://dx.doi.org/10.1051/rnd:2005031] [PMID: 16045890]
[92]
Kusu N, Laurikkala J, Imanishi M, et al. Sclerostin is a novel secreted osteoclast-derived bone morphogenetic protein antagonist with unique ligand specificity. J Biol Chem 2003; 278(26): 24113-7.
[http://dx.doi.org/10.1074/jbc.M301716200] [PMID: 12702725]
[93]
Tsiridis E, Upadhyay N, Giannoudis P. Molecular aspects of fracture healing: which are the important molecules? Injury 2007; 38(Suppl. 1): S11-25.
[http://dx.doi.org/10.1016/j.injury.2007.02.006] [PMID: 17383481]
[94]
Miyazono K, Kamiya Y, Morikawa M. Bone morphogenetic protein receptors and signal transduction. J Biochem 2010; 147(1): 35-51.
[http://dx.doi.org/10.1093/jb/mvp148] [PMID: 19762341]
[95]
Kessler E, Takahara K, Biniaminov L, Brusel M, Greenspan DS. Bone morphogenetic protein-1: The type I procollagen C-proteinase. Science 1996; 271(5247): 360-2.
[http://dx.doi.org/10.1126/science.271.5247.360] [PMID: 8553073]
[96]
Shen B, Bhargav D, Wei A, et al. BMP-13 emerges as a potential inhibitor of bone formation. Int J Biol Sci 2009; 5(2): 192-200.
[http://dx.doi.org/10.7150/ijbs.5.192] [PMID: 19240811]
[97]
Pecina M, Vukicevic S. Biological aspects of bone, cartilage and tendon regeneration. Int Orthop 2007; 31(6): 719-20.
[http://dx.doi.org/10.1007/s00264-007-0425-7] [PMID: 17704918]
[98]
Urist MR, Strates BS. The classic: Bone morphogenetic protein. Clin Orthop Relat Res 2009; 467(12): 3051-62.
[http://dx.doi.org/10.1007/s11999-009-1068-3] [PMID: 19727989]
[99]
Jäger M, Fischer J, Dohrn W, et al. Dexamethasone modulates BMP-2 effects on mesenchymal stem cells in vitro. J Orthop Res 2008; 26(11): 1440-8.
[http://dx.doi.org/10.1002/jor.20565] [PMID: 18404732]
[100]
Schwartz Z, Simon BJ, Duran MA, Barabino G, Chaudhri R, Boyan BD. Pulsed electromagnetic fields enhance BMP-2 dependent osteoblastic differentiation of human mesenchymal stem cells. J Orthop Res 2008; 26(9): 1250-5.
[http://dx.doi.org/10.1002/jor.20591] [PMID: 18404656]
[101]
Berasi SP, Varadarajan U, Archambault J, et al. Divergent activities of osteogenic BMP2, and tenogenic BMP12 and BMP13 independent of receptor binding affinities. Growth Factors 2011; 29(4): 128-39.
[http://dx.doi.org/10.3109/08977194.2011.593178] [PMID: 21702718]
[102]
Helvering LM, Sharp RL, Ou X, Geiser AG. Regulation of the promoters for the human bone morphogenetic protein 2 and 4 genes. Gene 2000; 256(1-2): 123-38.
[http://dx.doi.org/10.1016/S0378-1119(00)00364-4] [PMID: 11054542]
[103]
Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 1997; 390: 465-71.
[104]
Luo J, Tang M, Huang J, et al. TGFbeta/BMP type I receptors ALK1 and ALK2 are essential for BMP9-induced osteogenic signaling in mesenchymal stem cells. J Biol Chem 2010; 285(38): 29588-98.
[http://dx.doi.org/10.1074/jbc.M110.130518] [PMID: 20628059]
[105]
Avsian-Kretchmer O, Hsueh AJ. Comparative genomic analysis of the eight-membered ring cystine knot-containing bone morphogenetic protein antagonists. Mol Endocrinol 2004; 18(1): 1-12.
[http://dx.doi.org/10.1210/me.2003-0227] [PMID: 14525956]
[106]
Brunet LJ, McMahon JA, McMahon AP, Harland RM. Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton. Science 1998; 280(5368): 1455-7.
[http://dx.doi.org/10.1126/science.280.5368.1455] [PMID: 9603738]
[107]
Takayama K, Suzuki A, Manaka T, et al. RNA interference for noggin enhances the biological activity of bone morphogenetic proteins in vivo and in vitro. J Bone Miner Metab 2009; 27(4): 402-11.
[http://dx.doi.org/10.1007/s00774-009-0054-x] [PMID: 19252814]
[108]
Gazzerro E, Gangji V, Canalis E. Bone morphogenetic proteins induce the expression of noggin, which limits their activity in cultured rat osteoblasts. J Clin Invest 1998; 102(12): 2106-14.
[http://dx.doi.org/10.1172/JCI3459] [PMID: 9854046]
[109]
Rifas L. The role of noggin in human mesenchymal stem cell differentiation. J Cell Biochem 2007; 100(4): 824-34.
[http://dx.doi.org/10.1002/jcb.21132] [PMID: 17133353]
[110]
Zhang D, Ferguson CM, O’Keefe RJ, Puzas JE, Rosier RN, Reynolds PR. A role for the BMP antagonist chordin in endochondral ossification. J Bone Miner Res 2002; 17(2): 293-300.
[http://dx.doi.org/10.1359/jbmr.2002.17.2.293] [PMID: 11811560]
[111]
Hsu DR, Economides AN, Wang X, Eimon PM, Harland RM. The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. Mol Cell 1998; 1(5): 673-83.
[http://dx.doi.org/10.1016/S1097-2765(00)80067-2] [PMID: 9660951]
[112]
Topol LZ, Bardot B, Zhang Q, et al. Biosynthesis, post-translation modification, and functional characterization of Drm/Gremlin. J Biol Chem 2000; 275(12): 8785-93.
[http://dx.doi.org/10.1074/jbc.275.12.8785] [PMID: 10722723]
[113]
Wordinger RJ, Zode G, Clark AF. Focus on molecules: gremlin. Exp Eye Res 2008; 87(2): 78-9.
[http://dx.doi.org/10.1016/j.exer.2007.11.016] [PMID: 18201700]
[114]
Leijten JC, Bos SD, Landman EB, et al. GREM1, FRZB and DKK1 mRNA levels correlate with osteoarthritis and are regulated by osteoarthritis-associated factors. Arthritis Res Ther 2013; 15: R126.
[115]
Ideno H, Takanabe R, Shimada A, et al. Protein related to DAN and cerberus (PRDC) inhibits osteoblastic differentiation and its suppression promotes osteogenesis in vitro. Exp Cell Res 2009; 315(3): 474-84.
[http://dx.doi.org/10.1016/j.yexcr.2008.11.019] [PMID: 19073177]
[116]
Nilsson O, Parker EA, Hegde A, Chau M, Barnes KM, Baron J. Gradients in bone morphogenetic protein-related gene expression across the growth plate. J Endocrinol 2007; 193(1): 75-84.
[http://dx.doi.org/10.1677/joe.1.07099] [PMID: 17400805]
[117]
Matzuk MM, Lu N, Vogel H, Sellheyer K, Roop DR, Bradley A. Multiple defects and perinatal death in mice deficient in follistatin. Nature 1995; 374(6520): 360-3.
[http://dx.doi.org/10.1038/374360a0] [PMID: 7885475]
[118]
Shibanuma M, Mashimo J, Mita A, Kuroki T, Nose K. Cloning from a mouse osteoblastic cell line of a set of transforming-growth-factor-beta 1-regulated genes, one of which seems to encode a follistatin-related polypeptide. Eur J Biochem 1993; 217(1): 13-9.
[http://dx.doi.org/10.1111/j.1432-1033.1993.tb18212.x] [PMID: 7901004]
[119]
Mason ED, Konrad KD, Webb CD, Marsh JL. Dorsal midline fate in Drosophila embryos requires twisted gastrulation, a gene encoding a secreted protein related to human connective tissue growth factor. Genes Dev 1994; 8(13): 1489-501.
[http://dx.doi.org/10.1101/gad.8.13.1489] [PMID: 7958834]
[120]
Khattab HM, Kubota S, Takigawa M, et al. The BMP-2 mutant L51P: A BMP receptor IA binding-deficient inhibitor of noggin. J Bone Miner Metab 2019; 37: 199-205.
[PMID: 29667005]
[121]
Keller S, Nickel J, Zhang J-L, Sebald W, Mueller TD. Molecular recognition of BMP-2 and BMP receptor IA. Nat Struct Mol Biol 2004; 11(5): 481-8.
[http://dx.doi.org/10.1038/nsmb756] [PMID: 15064755]
[122]
Sebald HJ, Klenke FM, Siegrist M, Albers CE, Sebald W, Hofstetter W. Inhibition of endogenous antagonists with an engineered BMP-2 variant increases BMP-2 efficacy in rat femoral defect healing. Acta Biomater 2012; 8(10): 3816-20.
[http://dx.doi.org/10.1016/j.actbio.2012.06.036] [PMID: 22750247]
[123]
Khattab HM, Ono M, Sonoyama W, et al. The BMP2 antagonist inhibitor L51P enhances the osteogenic potential of BMP2 by simultaneous and delayed synergism. Bone 2014; 69: 165-73.
[http://dx.doi.org/10.1016/j.bone.2014.09.011] [PMID: 25240457]
[124]
Hauser M, Siegrist M, Denzer A, et al. Bisphosphonates reduce biomaterial turnover in healing of critical-size rat femoral defects. J Orthop Surg (Hong Kong) 2018; 262309499018802487
[125]
Albers CE, Hofstetter W, Sebald HJ, Sebald W, Siebenrock KA, Klenke FM. L51P - A BMP2 variant with osteoinductive activity via inhibition of Noggin. Bone 2012; 51(3): 401-6.
[http://dx.doi.org/10.1016/j.bone.2012.06.020] [PMID: 22750402]
[126]
Hauser M, Siegrist M, Keller I, Hofstetter W. Healing of fractures in osteoporotic bones in mice treated with bisphosphonates - A transcriptome analysis. Bone 2018; 112: 107-19.
[http://dx.doi.org/10.1016/j.bone.2018.04.017] [PMID: 29680263]
[127]
Reddi AH, Cunningham NS. Initiation and promotion of bone differentiation by bone morphogenetic proteins. J Bone Miner Res 1993; 8(Suppl. 2): S499-502.
[http://dx.doi.org/10.1002/jbmr.5650081313] [PMID: 8122519]
[128]
Sykaras N, Opperman LA. Bone morphogenetic proteins (BMPs): how do they function and what can they offer the clinician? J Oral Sci 2003; 45(2): 57-73.
[http://dx.doi.org/10.2334/josnusd.45.57] [PMID: 12930129]
[129]
Zhu W, Qiu Y, Sheng F, et al. An effective delivery vehicle of demineralized bone matrix incorporated with engineered collagen-binding human bone morphogenetic protein-2 to accelerate spinal fusion at low dose. J Mater Sci Mater Med 2017; 29(1): 2.
[http://dx.doi.org/10.1007/s10856-017-6007-3] [PMID: 29196819]
[130]
Alden TD, Pittman DD, Beres EJ, et al. Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy. J Neurosurg 1999; 90(1)(Suppl.): 109-14.
[PMID: 10413134]
[131]
Koerner JD, Markova DZ, Schroeder GD, et al. The local cytokine and growth factor response to rhBMP-2 after spinal fusion. Spine J 2018; 18: 1424-33.
[http://dx.doi.org/10.1016/j.spinee.2018.03.006] [PMID: 29550606]
[132]
Minamide A, Kawakami M, Hashizume H, Sakata R, Tamaki T. Evaluation of carriers of bone morphogenetic protein for spinal fusion. Spine 2001; 26(8): 933-9.
[http://dx.doi.org/10.1097/00007632-200104150-00017] [PMID: 11317116]
[133]
Helm GA, Alden TD, Beres EJ, et al. Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent. J Neurosurg 2000; 92(2)(Suppl.): 191-6.
[PMID: 10763690]
[134]
Abe E, Yamamoto M, Taguchi Y, et al. Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: antagonism by noggin. J Bone Miner Res 2000; 15(4): 663-73.
[http://dx.doi.org/10.1359/jbmr.2000.15.4.663] [PMID: 10780858]
[135]
Wan DC, Pomerantz JH, Brunet LJ, et al. Noggin suppression enhances in vitro osteogenesis and accelerates in vivo bone formation. J Biol Chem 2007; 282(36): 26450-9.
[http://dx.doi.org/10.1074/jbc.M703282200] [PMID: 17609215]
[136]
Klineberg E, Haudenschild DR, Snow KD, et al. The effect of noggin interference in a rabbit posterolateral spinal fusion model. Eur Spine J 2014; 23(11): 2385-92.
[http://dx.doi.org/10.1007/s00586-014-3252-8] [PMID: 24740279]
[137]
Devlin RD, Du Z, Pereira RC, et al. Skeletal overexpression of noggin results in osteopenia and reduced bone formation. Endocrinology 2003; 144(5): 1972-8.
[http://dx.doi.org/10.1210/en.2002-220918] [PMID: 12697704]
[138]
Okamoto M, Murai J, Yoshikawa H, Tsumaki N. Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. J Bone Miner Res 2006; 21(7): 1022-33.
[http://dx.doi.org/10.1359/jbmr.060411] [PMID: 16813523]
[139]
Tsuji K, Cox K, Bandyopadhyay A, Harfe BD, Tabin CJ, Rosen V. BMP4 is dispensable for skeletogenesis and fracture-healing in the limb. J Bone Joint Surg Am 2008; 90(Suppl. 1): 14-8.
[http://dx.doi.org/10.2106/JBJS.G.01109] [PMID: 18292351]
[140]
Suzuki D, Yamada A, Aizawa R, et al. BMP2 differentially regulates the expression of Gremlin1 and Gremlin2, the negative regulators of BMP function, during osteoblast differentiation. Calcif Tissue Int 2012; 91(1): 88-96.
[http://dx.doi.org/10.1007/s00223-012-9614-5] [PMID: 22644325]
[141]
Boden SD, Kang J, Sandhu H, Heller JG. Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial: 2002 Volvo Award in clinical studies. Spine 2002; 27(23): 2662-73.
[http://dx.doi.org/10.1097/00007632-200212010-00005] [PMID: 12461392]
[142]
Friedlaender GE, Perry CR, Cole JD, et al. Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am 2001; 83-A(Pt 2)(Suppl. 1): S151-8.
[http://dx.doi.org/10.2106/00004623-200100002-00010] [PMID: 11314793]
[143]
Tang Y, Ye X, Klineberg EO, Curtiss S, Maitra S, Gupta MC. Temporal and spatial expression of BMPs and BMP antagonists during posterolateral lumbar fusion. Spine 2011; 36(4): E237-44.
[PMID: 21099737]
[144]
Kwong FN, Hoyland JA, Evans CH, Freemont AJ. Regional and cellular localisation of BMPs and their inhibitors’ expression in human fractures. Int Orthop 2009; 33(1): 281-8.
[http://dx.doi.org/10.1007/s00264-008-0691-z] [PMID: 19023570]
[145]
Fajardo M, Liu CJ, Egol K. Levels of expression for BMP-7 and several BMP antagonists may play an integral role in a fracture nonunion: a pilot study. Clin Orthop Relat Res 2009; 467(12): 3071-8.
[http://dx.doi.org/10.1007/s11999-009-0981-9] [PMID: 19597895]
[146]
Niikura T, Hak DJ, Reddi AH. Global gene profiling reveals a downregulation of BMP gene expression in experimental atrophic nonunions compared to standard healing fractures. J Orthop Res 2006; 24(7): 1463-71.
[http://dx.doi.org/10.1002/jor.20182] [PMID: 16705710]
[147]
Dean DB, Watson JT, Jin W, et al. Distinct functionalities of bone morphogenetic protein antagonists during fracture healing in mice. J Anat 2010; 216(5): 625-30.
[http://dx.doi.org/10.1111/j.1469-7580.2010.01214.x] [PMID: 20298438]
[148]
Kwong FN, Hoyland JA, Freemont AJ, Evans CH. Altered relative expression of BMPs and BMP inhibitors in cartilaginous areas of human fractures progressing towards nonunion. J Orthop Res 2009; 27(6): 752-7.
[http://dx.doi.org/10.1002/jor.20794] [PMID: 19058174]
[149]
Yoshimura Y, Nomura S, Kawasaki S, Tsutsumimoto T, Shimizu T, Takaoka K. Colocalization of noggin and bone morphogenetic protein-4 during fracture healing. J Bone Miner Res 2001; 16(5): 876-84.
[http://dx.doi.org/10.1359/jbmr.2001.16.5.876] [PMID: 11341332]
[150]
Kishigami S, Mishina Y. BMP signaling and early embryonic patterning. Cytokine Growth Factor Rev 2005; 16(3): 265-78.
[http://dx.doi.org/10.1016/j.cytogfr.2005.04.002] [PMID: 15871922]
[151]
Chen C, Uludağ H, Wang Z, Jiang H. Noggin suppression decreases BMP-2-induced osteogenesis of human bone marrow-derived mesenchymal stem cells in vitro. J Cell Biochem 2012; 113(12): 3672-80.
[http://dx.doi.org/10.1002/jcb.24240] [PMID: 22740073]
[152]
Kwong FNK, Richardson SM, Evans CH. Chordin knockdown enhances the osteogenic differentiation of human mesenchymal stem cells. Arthritis Res Ther 2008; 10(3): R65.
[http://dx.doi.org/10.1186/ar2436] [PMID: 18533030]
[153]
Wang C, Xiao F, Gan Y, et al. Improving Bone Regeneration Using Chordin siRNA Delivered by pH-Responsive and Non-Toxic Polyspermine Imidazole-4,5-Imine. Cell Physiol Biochem 2018; 46(1): 133-47.
[http://dx.doi.org/10.1159/000488416] [PMID: 29587276]
[154]
Hasharoni A, Zilberman Y, Turgeman G, Helm GA, Liebergall M, Gazit D. Murine spinal fusion induced by engineered mesenchymal stem cells that conditionally express bone morphogenetic protein-2. J Neurosurg Spine 2005; 3(1): 47-52.
[http://dx.doi.org/10.3171/spi.2005.3.1.0047] [PMID: 16122022]
[155]
Wang JC, Kanim LE, Yoo S, Campbell PA, Berk AJ, Lieberman JR. Effect of regional gene therapy with bone morphogenetic protein-2-producing bone marrow cells on spinal fusion in rats. J Bone Joint Surg Am 2003; 85(5): 905-11.
[http://dx.doi.org/10.2106/00004623-200305000-00020] [PMID: 12728043]
[156]
Riew KD, Wright NM, Cheng S, Avioli LV, Lou J. Induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene in a rabbit spinal fusion model. Calcif Tissue Int 1998; 63(4): 357-60.
[http://dx.doi.org/10.1007/s002239900540] [PMID: 9744997]
[157]
Cheng SL, Lou J, Wright NM, et al. In vitro and in vivo induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene. Calcif Tissue Int 2001; 68: 87-94.
[http://dx.doi.org/10.1007/BF02678146]
[158]
Dragoo JL, Choi JY, Lieberman JR, et al. Bone induction by BMP-2 transduced stem cells derived from human fat. J Orthop Res 2003; 21(4): 622-9.
[http://dx.doi.org/10.1016/S0736-0266(02)00238-3] [PMID: 12798061]
[159]
Wang L, Huang Y, Pan K, Jiang X, Liu C. Osteogenic responses to different concentrations/ratios of BMP-2 and bFGF in bone formation. Ann Biomed Eng 2010; 38(1): 77-87.
[http://dx.doi.org/10.1007/s10439-009-9841-8] [PMID: 19921434]
[160]
Sheyn D, Pelled G, Zilberman Y, et al. Nonvirally engineered porcine adipose tissue-derived stem cells: use in posterior spinal fusion. Stem Cells 2008; 26(4): 1056-64.
[http://dx.doi.org/10.1634/stemcells.2007-0858] [PMID: 18218819]
[161]
Friedman MS, Long MW, Hankenson KD. Osteogenic differentiation of human mesenchymal stem cells is regulated by bone morphogenetic protein-6. J Cell Biochem 2006; 98(3): 538-54.
[http://dx.doi.org/10.1002/jcb.20719] [PMID: 16317727]
[162]
Hannallah D, Peng H, Young B, Usas A, Gearhart B, Huard J. Retroviral delivery of Noggin inhibits the formation of heterotopic ossification induced by BMP-4, demineralized bone matrix, and trauma in an animal model. J Bone Joint Surg Am 2004; 86(1): 80-91.
[http://dx.doi.org/10.2106/00004623-200401000-00013] [PMID: 14711949]
[163]
Diefenderfer DL, Osyczka AM, Reilly GC, Leboy PS. BMP responsiveness in human mesenchymal stem cells. Connect Tissue Res 2003; 44(Suppl. 1): 305-11.
[http://dx.doi.org/10.1080/03008200390181825] [PMID: 12952214]
[164]
Hu K, Sun H, Gui B, et al. Gremlin-1 suppression increases BMP-2-induced osteogenesis of human mesenchymal stem cells. Mol Med Rep 2017; 15(4): 2186-94.
[http://dx.doi.org/10.3892/mmr.2017.6253] [PMID: 28260028]
[165]
Ramasubramanian A, Shiigi S, Lee GK, et al. Non-viral delivery of inductive and suppressive genes to adipose-derived stem cells for osteogenic differentiation. Pharm Res 2011; 28(6): 1328-37.
[http://dx.doi.org/10.1007/s11095-011-0406-9] [PMID: 21424160]
[166]
Fan J, Park H, Tan S, et al. Enhanced osteogenesis of adipose derived stem cells with Noggin suppression and delivery of BMP-2. PLoS One 2013; 8(8)e72474
[http://dx.doi.org/10.1371/journal.pone.0072474] [PMID: 23977305]
[167]
Willems N, Bach FC, Plomp SG, et al. Intradiscal application of rhBMP-7 does not induce regeneration in a canine model of spontaneous intervertebral disc degeneration. Arthritis Res Ther 2015; 17: 137.
[http://dx.doi.org/10.1186/s13075-015-0625-2] [PMID: 26013758]
[168]
Haschtmann D, Ferguson SJ, Stoyanov JV. BMP-2 and TGF-β3 do not prevent spontaneous degeneration in rabbit disc explants but induce ossification of the annulus fibrosus. Eur Spine J 2012; 21(9): 1724-33.
[http://dx.doi.org/10.1007/s00586-012-2371-3] [PMID: 22639297]
[169]
Li J, Yoon ST, Hutton WC. Effect of bone morphogenetic protein-2 (BMP-2) on matrix production, other BMPs, and BMP receptors in rat intervertebral disc cells. J Spinal Disord Tech 2004; 17(5): 423-8.
[http://dx.doi.org/10.1097/01.bsd.0000112084.85112.5d] [PMID: 15385883]
[170]
Li Z, Lang G, Karfeld-Sulzer LS, et al. Heterodimeric BMP-2/7 for nucleus pulposus regeneration-In vitro and ex vivo studies. J Orthop Res 2017; 35(1): 51-60.
[http://dx.doi.org/10.1002/jor.23351] [PMID: 27340938]
[171]
Kim DJ, Moon SH, Kim H, et al. Bone morphogenetic protein-2 facilitates expression of chondrogenic, not osteogenic, phenotype of human intervertebral disc cells. Spine 2003; 28(24): 2679-84.
[http://dx.doi.org/10.1097/01.BRS.0000101445.46487.16] [PMID: 14673369]
[172]
Lee KI, Moon SH, Kim H, et al. Tissue engineering of the intervertebral disc with cultured nucleus pulposus cells using atelocollagen scaffold and growth factors. Spine 2012; 37(6): 452-8.
[http://dx.doi.org/10.1097/BRS.0b013e31823c8603] [PMID: 22037529]
[173]
Wei A, Brisby H, Chung SA, Diwan AD. Bone morphogenetic protein-7 protects human intervertebral disc cells in vitro from apoptosis. Spine J 2008; 8(3): 466-74.
[http://dx.doi.org/10.1016/j.spinee.2007.04.021] [PMID: 18082466]
[174]
Resnick D, Guerra J Jr, Robinson CA, Vint VC. Association of diffuse idiopathic skeletal hyperostosis (DISH) and calcification and ossification of the posterior longitudinal ligament. AJR Am J Roentgenol 1978; 131(6): 1049-53.
[http://dx.doi.org/10.2214/ajr.131.6.1049] [PMID: 104572]
[175]
Kuperus JS, Westerveld LA, Rutges JP, et al. Histological characteristics of diffuse idiopathic skeletal hyperostosis. J Orthop Res 2017; 35(1): 140-6.
[http://dx.doi.org/10.1002/jor.23267] [PMID: 27101345]
[176]
Karamouzian S, Eskandary H, Faramarzee M, et al. Frequency of lumbar intervertebral disc calcification and angiogenesis, and their correlation with clinical, surgical, and magnetic resonance imaging findings. Spine 2010; 35(8): 881-6.
[http://dx.doi.org/10.1097/BRS.0b013e3181b9c986] [PMID: 20354479]
[177]
Tekari A, May RD, Frauchiger DA, Chan SC, Benneker LM, Gantenbein B. The BMP2 variant L51P restores the osteogenic differentiation of human mesenchymal stromal cells in the presence of intervertebral disc cells. Eur Cell Mater 2017; 33: 197-210.
[http://dx.doi.org/10.22203/eCM.v033a15] [PMID: 28266688]
[178]
Imai Y, Miyamoto K, An HS, Thonar EJ, Andersson GB, Masuda K. Recombinant human osteogenic protein-1 upregulates proteoglycan metabolism of human anulus fibrosus and nucleus pulposus cells. Spine 2007; 32(12): 1303-9.
[http://dx.doi.org/10.1097/BRS.0b013e3180593238] [PMID: 17515818]
[179]
Leckie SK, Bechara BP, Hartman RA, et al. Injection of AAV2-BMP2 and AAV2-TIMP1 into the nucleus pulposus slows the course of intervertebral disc degeneration in an in vivo rabbit model. Spine J 2012; 12(1): 7-20.
[http://dx.doi.org/10.1016/j.spinee.2011.09.011] [PMID: 22023960]
[180]
Huang KY, Yan JJ, Hsieh CC, Chang MS, Lin RM. The in vivo biological effects of intradiscal recombinant human bone morphogenetic protein-2 on the injured intervertebral disc: an animal experiment. Spine 2007; 32(11): 1174-80.
[http://dx.doi.org/10.1097/01.brs.0000263369.95182.19] [PMID: 17495773]
[181]
Masuda K, Imai Y, Okuma M, et al. Osteogenic protein-1 injection into a degenerated disc induces the restoration of disc height and structural changes in the rabbit anular puncture model. Spine 2006; 31(7): 742-54.
[http://dx.doi.org/10.1097/01.brs.0000206358.66412.7b] [PMID: 16582847]
[182]
An HS, Takegami K, Kamada H, et al. Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits. Spine 2005; 30(1): 25-31.
[http://dx.doi.org/10.1097/01.brs.0000148002.68656.4d] [PMID: 15626976]
[183]
Masuda K, Takegami K, An H, et al. Recombinant osteogenic protein-1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells cultured in alginate beads. J Orthop Res 2003; 21(5): 922-30.
[http://dx.doi.org/10.1016/S0736-0266(03)00037-8] [PMID: 12919882]
[184]
Tim Yoon S, Su Kim K, Li J, et al. The effect of bone morphogenetic protein-2 on rat intervertebral disc cells in vitro. Spine 2003; 28(16): 1773-80.
[http://dx.doi.org/10.1097/01.BRS.0000083204.44190.34] [PMID: 12923462]
[185]
Zara JN, Siu RK, Zhang X, et al. High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo. Tissue Eng Part A 2011; 17(9-10): 1389-99.
[http://dx.doi.org/10.1089/ten.tea.2010.0555] [PMID: 21247344]
[186]
Osyczka AM, Diefenderfer DL, Bhargave G, Leboy PS. Different effects of BMP-2 on marrow stromal cells from human and rat bone. Cells Tissues Organs (Print) 2004; 176(1-3): 109-19.
[http://dx.doi.org/10.1159/000075032] [PMID: 14745240]
[187]
Gruber R, Graninger W, Bobacz K, Watzek G, Erlacher L. BMP-6-induced osteogenic differentiation of mesenchymal cell lines is not modulated by sex steroids and resveratrol. Cytokine 2003; 23(4-5): 133-7.
[http://dx.doi.org/10.1016/S1043-4666(03)00223-0] [PMID: 12967649]


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Article Details

VOLUME: 14
ISSUE: 8
Year: 2019
Page: [618 - 643]
Pages: 26
DOI: 10.2174/1574888X14666190628103528

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