Exosomes and Bone Disease

Author(s): Su-Kang Shan, Xiao Lin, Fuxingzi Li, Feng Xu, Jia-Yu Zhong, Bei Guo, Yi Wang, Ming-Hui Zheng, Feng Wu, Ling-Qing Yuan*

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 42 , 2019

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Exosomes, which mediate cell-to-cell communications and provide a novel insight into information exchange, have drawn increasing attention in recent years. The homeostasis of bone metabolism is critical for bone health. The most common bone diseases such as osteoporosis, osteoarthritis and bone fractures have apparent correlations with exosomes. Accumulating evidence has suggested the potential regenerative capacities of stem cell-derived exosomes. In this review, we summarise the pathophysiological mechanism, clinical picture and therapeutic effects of exosomes in bone metabolism. We introduce the advantages and challenges in the application of exosomes. Although the exact mechanisms remain unclear, miRNAs seem to play major roles in the exosome.

Keywords: Exosomes, microRNAs, osteoporosis, osteoarthritis, fracture healing, regeneration.

van der Pol E, Böing AN, Harrison P, Sturk A, Nieuwland R. Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev 2012; 64(3): 676-705.
[http://dx.doi.org/10.1124/pr.112.005983] [PMID: 22722893]
Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D. Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell 2016; 30(6): 836-48.
[http://dx.doi.org/10.1016/j.ccell.2016.10.009] [PMID: 27960084]
Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002; 2(8): 569-79.
[http://dx.doi.org/10.1038/nri855] [PMID: 12154376]
Cocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artefacts no more. Trends Cell Biol 2009; 19(2): 43-51.
[http://dx.doi.org/10.1016/j.tcb.2008.11.003] [PMID: 19144520]
Muralidharan-Chari V, Clancy JW, Sedgwick A, D’Souza-Schorey C. Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci 2010; 123(Pt 10): 1603-11.
[http://dx.doi.org/10.1242/jcs.064386] [PMID: 20445011]
Pap E, Pállinger E, Pásztói M, Falus A. Highlights of a new type of intercellular communication: microvesicle-based information transfer. Inflamm Res 2009; 58(1): 1-8.
[http://dx.doi.org/10.1007/s00011-008-8210-7] [PMID: 19132498]
Balch WE, Dunphy WG, Braell WA, Rothman JE. Reconstitution of the transport of protein between successive compartments of the Golgi measured by the coupled incorporation of N-acetylglucosamine. Cell 1984; 39(2 Pt 1): 405-16.
[http://dx.doi.org/10.1016/0092-8674(84)90019-9] [PMID: 6498939]
Novick P, Schekman R. Secretion and cell-surface growth are blocked in a temperature-sensitive mutant of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 1979; 76(4): 1858-62.
[http://dx.doi.org/10.1073/pnas.76.4.1858] [PMID: 377286]
Perin MS, Fried VA, Mignery GA, Jahn R, Südhof TC. Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C. Nature 1990; 345(6272): 260-3.
[http://dx.doi.org/10.1038/345260a0] [PMID: 2333096]
Lindenbergh MFS, Stoorvogel W. Antigen presentation by extracellular vesicles from professional antigen-presenting cells. Annu Rev Immunol 2018; 36: 435-59.
[http://dx.doi.org/10.1146/annurev-immunol-041015-055700] [PMID: 29400984]
Graner MW, Schnell S, Olin MR. Tumor-derived exosomes, microRNAs, and cancer immune suppression. Semin Immunopathol 2018; 40(5): 505-15.
[http://dx.doi.org/10.1007/s00281-018-0689-6] [PMID: 29869058]
Ludwig S, Floros T, Theodoraki MN, et al. Suppression of lymphocyte functions by plasma exosomes correlates with disease activity in patients with head and neck cancer. Clin Cancer Res 2017; 23(16): 4843-54.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2819] [PMID: 28400428]
Desrochers LM, Antonyak MA, Cerione RA. Extracellular vesicles: satellites of information transfer in cancer and stem cell biology. Dev Cell 2016; 37(4): 301-9.
[http://dx.doi.org/10.1016/j.devcel.2016.04.019] [PMID: 27219060]
Katsimbri P. The biology of normal bone remodelling. Eur J Cancer Care (Engl) 2017; 26(6): 26.
[http://dx.doi.org/10.1111/ecc.12740] [PMID: 28786518]
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]
Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet 2003; 4(8): 638-49.
[http://dx.doi.org/10.1038/nrg1122] [PMID: 12897775]
NIH consensus development panel on osteoporosis prevention, diagnosis, and therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001; 285(6): 785-95.
[http://dx.doi.org/10.1001/jama.285.6.785] [PMID: 11176917]
Armas LA, Recker RR. Pathophysiology of osteoporosis: new mechanistic insights. Endocrinol Metab Clin North Am 2012; 41(3): 475-86.
[http://dx.doi.org/10.1016/j.ecl.2012.04.006] [PMID: 22877425]
Li G, Thabane L, Papaioannou A, Ioannidis G, Levine MA, Adachi JD. An overview of osteoporosis and frailty in the elderly. BMC Musculoskelet Disord 2017; 18(1): 46.
[http://dx.doi.org/10.1186/s12891-017-1403-x] [PMID: 28125982]
Lin X, Xiong D, Peng YQ, et al. Epidemiology and management of osteoporosis in the People’s Republic of China: current perspectives. Clin Interv Aging 2015; 10: 1017-33.
[PMID: 26150706]
Shan PF, Wu XP, Zhang H, Cao XZ, Yuan LQ, Liao EY. Age-related bone mineral density, osteoporosis rate and risk of vertebral fracture in mainland Chinese women with type 2 diabetes mellitus. J Endocrinol Invest 2011; 34(3): 190-6.
[http://dx.doi.org/10.1007/BF03347065] [PMID: 20808073]
Lizneva D, Yuen T, Sun L, et al. Emerging concepts in the epidemiology, pathophysiology, and clinical care of osteoporosis across the menopausal transition. Matrix Biol 2018; 71-72: 70-81.
[http://dx.doi.org/10.1016/j.matbio.2018.05.001] [PMID: 29738833]
Li WF, Hou SX, Yu B, Li MM, Férec C, Chen JM. Genetics of osteoporosis: accelerating pace in gene identification and validation. Hum Genet 2010; 127(3): 249-85.
[http://dx.doi.org/10.1007/s00439-009-0773-z] [PMID: 20101412]
Zhu X, Jiang Y, Shan PF, et al. Vaspin attenuates the apoptosis of human osteoblasts through ERK signaling pathway. Amino Acids 2013; 44(3): 961-8.
[http://dx.doi.org/10.1007/s00726-012-1425-5] [PMID: 23135225]
Liu Y, Xu F, Pei HX, et al. Vaspin regulates the osteogenic differentiation of MC3T3-E1 through the PI3K-Akt/miR-34c loop. Sci Rep 2016; 6: 25578.
[http://dx.doi.org/10.1038/srep25578] [PMID: 27156573]
Wu SS, Liang QH, Liu Y, Cui RR, Yuan LQ, Liao EY. Omentin-1 stimulates human osteoblast proliferation through PI3K/Akt signal pathway. Int J Endocrinol 2013; 2013(4) 368970
[http://dx.doi.org/10.1155/2013/368970] [PMID: 23606838]
Xie Y, Hu JH, Wu H, Huang ZZ, Yan HW, Shi ZY. Bone marrow stem cells derived exosomes improve osteoporosis by promoting osteoblast proliferation and inhibiting cell apoptosis. Eur Rev Med Pharmacol Sci 2019; 23(3): 1214-20.
[PMID: 30779091]
Li H, Liu D, Li C, et al. Exosomes secreted from mutant-HIF-1α-modified bone-marrow-derived mesenchymal stem cells attenuate early steroid-induced avascular necrosis of femoral head in rabbit. Cell Biol Int 2017; 41(12): 1379-90.
[http://dx.doi.org/10.1002/cbin.10869] [PMID: 28877384]
Qin Y, Wang L, Gao Z, Chen G, Zhang C. Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo. Sci Rep 2016; 6: 21961.
[http://dx.doi.org/10.1038/srep21961] [PMID: 26911789]
Zuo R, Liu M, Wang Y, et al. BM-MSC-derived exosomes alleviate radiation-induced bone loss by restoring the function of recipient BM-MSCs and activating Wnt/β-catenin signaling. Stem Cell Res Ther 2019; 10(1): 30.
[http://dx.doi.org/10.1186/s13287-018-1121-9] [PMID: 30646958]
Qi X, Zhang J, Yuan H, et al. Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats. Int J Biol Sci 2016; 12(7): 836-49.
[http://dx.doi.org/10.7150/ijbs.14809] [PMID: 27313497]
Hu Y, Xu R, Chen CY, et al. Extracellular vesicles from human umbilical cord blood ameliorate bone loss in senile osteoporotic mice. Metabolism 2019; 95: 93-101.
[http://dx.doi.org/10.1016/j.metabol.2019.01.009] [PMID: 30668962]
Ge M, Ke R, Cai T, Yang J, Mu X. Identification and proteomic analysis of osteoblast-derived exosomes. Biochem Biophys Res Commun 2015; 467(1): 27-32.
[http://dx.doi.org/10.1016/j.bbrc.2015.09.135] [PMID: 26420226]
Cui Y, Luan J, Li H, Zhou X, Han J. Exosomes derived from mineralizing osteoblasts promote ST2 cell osteogenic differentiation by alteration of microRNA expression. FEBS Lett 2016; 590(1): 185-92.
[http://dx.doi.org/10.1002/1873-3468.12024] [PMID: 26763102]
Weilner S, Schraml E, Wieser M, et al. Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells. Aging Cell 2016; 15(4): 744-54.
[http://dx.doi.org/10.1111/acel.12484] [PMID: 27146333]
Xie Y, Gao Y, Zhang L, Chen Y, Ge W, Tang P. Involvement of serum-derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone-related proteins. Aging Cell 2018; 17(3) e12758
[http://dx.doi.org/10.1111/acel.12758] [PMID: 29603567]
Song H, Li X, Zhao Z, et al. Reversal of osteoporotic activity by endothelial cell-secreted bone targeting and biocompatible exosomes. Nano Lett 2019; 19(5): 3040-8.
[http://dx.doi.org/10.1021/acs.nanolett.9b00287] [PMID: 30968694]
Cui Y, Fu S, Sun D, Xing J, Hou T, Wu X. EPC-derived exosomes promote osteoclastogenesis through LncRNA-MALAT1. J Cell Mol Med 2019; 23(6): 3843-54.
[http://dx.doi.org/10.1111/jcmm.14228] [PMID: 31025509]
Ekström K, Omar O, Granéli C, Wang X, Vazirisani F, Thomsen P. Monocyte exosomes stimulate the osteogenic gene expression of mesenchymal stem cells. PLoS One 2013; 8(9) e75227
[http://dx.doi.org/10.1371/journal.pone.0075227] [PMID: 24058665]
Li D, Liu J, Guo B, et al. Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nat Commun 2016; 7: 10872.
[http://dx.doi.org/10.1038/ncomms10872] [PMID: 26947250]
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]
Brady RD, Shultz SR, Sun M, et al. Experimental traumatic brain injury induces bone loss in rats. J Neurotrauma 2016; 33(23): 2154-60.
[http://dx.doi.org/10.1089/neu.2014.3836] [PMID: 25686841]
Xu R, Shen X, Si Y, et al. MicroRNA-31a-5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment. Aging Cell 2018; 17(4) e12794
[http://dx.doi.org/10.1111/acel.12794] [PMID: 29896785]
Huynh N, VonMoss L, Smith D, et al. Characterization of regulatory extracellular vesicles from osteoclasts. J Dent Res 2016; 95(6): 673-9.
[http://dx.doi.org/10.1177/0022034516633189] [PMID: 26908631]
Sato M, Suzuki T, Kawano M, Tamura M. Circulating osteocyte-derived exosomes contain miRNAs which are enriched in exosomes from MLO-Y4 cells. Biomed Rep 2017; 6(2): 223-31.
[http://dx.doi.org/10.3892/br.2016.824] [PMID: 28357077]
Qin Y, Peng Y, Zhao W, et al. Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: a novel mechanism in muscle-bone communication. J Biol Chem 2017; 292(26): 11021-33.
[http://dx.doi.org/10.1074/jbc.M116.770941] [PMID: 28465350]
Ren L, Song ZJ, Cai QW, et al. Adipose mesenchymal stem cell-derived exosomes ameliorate hypoxia/serum deprivation-induced osteocyte apoptosis and osteocyte-mediated osteoclastogenesis in vitro. Biochem Biophys Res Commun 2019; 508(1): 138-44.
[http://dx.doi.org/10.1016/j.bbrc.2018.11.109] [PMID: 30473217]
Kuang MJ, Huang Y, Zhao XG, et al. Exosomes derived from Wharton’s jelly of human umbilical cord mesenchymal stem cells reduce osteocyte apoptosis in glucocorticoid-induced osteonecrosis of the femoral head in rats via the miR-21-PTEN-AKT signalling pathway. Int J Biol Sci 2019; 15(9): 1861-71.
[http://dx.doi.org/10.7150/ijbs.32262] [PMID: 31523188]
DeLise AM, Fischer L, Tuan RS. Cellular interactions and signaling in cartilage development. Osteoarthritis Cartilage 2000; 8(5): 309-34.
[http://dx.doi.org/10.1053/joca.1999.0306] [PMID: 10966838]
Akiyama H, Chaboissier MC, Martin JF, Schedl A, de Crombrugghe B. The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev 2002; 16(21): 2813-28.
[http://dx.doi.org/10.1101/gad.1017802] [PMID: 12414734]
Ikeda T, Kamekura S, Mabuchi A, et al. The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals sufficient for induction of permanent cartilage. Arthritis Rheum 2004; 50(11): 3561-73.
[http://dx.doi.org/10.1002/art.20611] [PMID: 15529345]
Tetlow LC, Adlam DJ, Woolley DE. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis Rheum 2001; 44(3): 585-94.
[http://dx.doi.org/10.1002/1529-0131(200103)44:3<585:AID-ANR107>3.0.CO;2-C] [PMID: 11263773]
Clements KM, Flannelly JK, Tart J, et al. Matrix metalloproteinase 17 is necessary for cartilage aggrecan degradation in an inflammatory environment. Ann Rheum Dis 2011; 70(4): 683-9.
[http://dx.doi.org/10.1136/ard.2010.130757] [PMID: 21216815]
Goldring MB, Otero M, Plumb DA, et al. Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. Eur Cell Mater 2011; 21: 202-20.
[http://dx.doi.org/10.22203/eCM.v021a16] [PMID: 21351054]
Fosang AJ, Last K, Knäuper V, Murphy G, Neame PJ. Degradation of cartilage aggrecan by collagenase-3 (MMP-13). FEBS Lett 1996; 380(1-2): 17-20.
[http://dx.doi.org/10.1016/0014-5793(95)01539-6] [PMID: 8603731]
Wang T, He C. Pro-inflammatory cytokines: The link between obesity and osteoarthritis. Cytokine Growth Factor Rev 2018; 44: 38-50.
[http://dx.doi.org/10.1016/j.cytogfr.2018.10.002] [PMID: 30340925]
McAlindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage 2014; 22(3): 363-88.
[http://dx.doi.org/10.1016/j.joca.2014.01.003] [PMID: 24462672]
McGrory B, Weber K, Lynott JA, et al. The American Academy of Orthopaedic Surgeons Evidence-Based Clinical Practice Guideline on Surgical Management of Osteoarthritis of the Knee. J Bone Joint Surg Am 2016; 98(8): 688-92.
[http://dx.doi.org/10.2106/JBJS.15.01311] [PMID: 27098328]
Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med 2013; 41(2): 356-64.
[http://dx.doi.org/10.1177/0363546512471299] [PMID: 23299850]
Rabago D, Patterson JJ, Mundt M, et al. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med 2013; 11(3): 229-37.
[http://dx.doi.org/10.1370/afm.1504] [PMID: 23690322]
Abate M, Vanni D, Pantalone A, Salini V. Hyaluronic acid in knee osteoarthritis: preliminary results using a four months administration schedule. Int J Rheum Dis 2017; 20(2): 199-202.
[http://dx.doi.org/10.1111/1756-185X.12572] [PMID: 25944257]
Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994; 331(14): 889-95.
[http://dx.doi.org/10.1056/NEJM199410063311401] [PMID: 8078550]
Jevotovsky DS, Alfonso AR, Einhorn TA, Chiu ES. Osteoarthritis and stem cell therapy in humans: a systematic review. Osteoarthritis Cartilage 2018; 26(6): 711-29.
[http://dx.doi.org/10.1016/j.joca.2018.02.906] [PMID: 29544858]
Toh WS, Lai RC, Hui JHP, Lim SK. MSC exosome as a cell-free MSC therapy for cartilage regeneration: implications for osteoarthritis treatment. Semin Cell Dev Biol 2017; 67: 56-64.
[http://dx.doi.org/10.1016/j.semcdb.2016.11.008] [PMID: 27871993]
Vonk LA, van Dooremalen SFJ, Liv N, et al. Mesenchymal stromal/stem cell-derived extracellular vesicles promote human cartilage regeneration in vitro. Theranostics 2018; 8(4): 906-20.
[http://dx.doi.org/10.7150/thno.20746] [PMID: 29463990]
Cosenza S, Ruiz M, Toupet K, Jorgensen C, Noël D. Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci Rep 2017; 7(1): 16214.
[http://dx.doi.org/10.1038/s41598-017-15376-8] [PMID: 29176667]
Tofiño-Vian M, Guillén MI, Pérez Del Caz MD, Silvestre A, Alcaraz MJ. Microvesicles from human adipose tissue-derived mesenchymal stem cells as a new protective strategy in osteoarthritic chondrocytes. Cell Physiol Biochem 2018; 47(1): 11-25.
[http://dx.doi.org/10.1159/000489739] [PMID: 29763932]
Zhang S, Chu WC, Lai RC, Lim SK, Hui JH, Toh WS. Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthritis Cartilage 2016; 24(12): 2135-40.
[http://dx.doi.org/10.1016/j.joca.2016.06.022] [PMID: 27390028]
Wang Y, Yu D, Liu Z, et al. Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix. Stem Cell Res Ther 2017; 8(1): 189.
[http://dx.doi.org/10.1186/s13287-017-0632-0] [PMID: 28807034]
Liu Y, Zou R, Wang Z, Wen C, Zhang F, Lin F. Exosomal KLF3-AS1 from hMSCs promoted cartilage repair and chondrocyte proliferation in osteoarthritis. Biochem J 2018; 475(22): 3629-38.
[http://dx.doi.org/10.1042/BCJ20180675] [PMID: 30341166]
Liu Y, Lin L, Zou R, Wen C, Wang Z, Lin F. MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis. Cell Cycle 2018; 17(21-22): 2411-22.
[http://dx.doi.org/10.1080/15384101.2018.1526603] [PMID: 30324848]
Tofiño-Vian M, Guillén MI, Pérez Del Caz MD, Castejón MA, Alcaraz MJ. Extracellular vesicles from adipose-derived mesenchymal stem cells downregulate senescence features in osteoarthritic osteoblasts. Oxid Med Cell Longev 2017; 2017 7197598
[http://dx.doi.org/10.1155/2017/7197598] [PMID: 29230269]
Zhang S, Teo KYW, Chuah SJ, Lai RC, Lim SK, Toh WS. MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis. Biomaterials 2019; 200: 35-47.
[http://dx.doi.org/10.1016/j.biomaterials.2019.02.006] [PMID: 30771585]
Wu J, Kuang L, Chen C, et al. miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis. Biomaterials 2019; 206: 87-100.
[http://dx.doi.org/10.1016/j.biomaterials.2019.03.022] [PMID: 30927715]
Zhu Y, Wang Y, Zhao B, et al. Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis. Stem Cell Res Ther 2017; 8(1): 64.
[http://dx.doi.org/10.1186/s13287-017-0510-9] [PMID: 28279188]
Mao G, Hu S, Zhang Z, et al. Exosomal miR-95-5p regulates chondrogenesis and cartilage degradation via histone deacetylase 2/8. J Cell Mol Med 2018; 22(11): 5354-66.
[http://dx.doi.org/10.1111/jcmm.13808] [PMID: 30063117]
Mao G, Zhang Z, Hu S, et al. Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A. Stem Cell Res Ther 2018; 9(1): 247.
[http://dx.doi.org/10.1186/s13287-018-1004-0] [PMID: 30257711]
Tao SC, Yuan T, Zhang YL, Yin WJ, Guo SC, Zhang CQ. Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics 2017; 7(1): 180-95.
[http://dx.doi.org/10.7150/thno.17133] [PMID: 28042326]
Murata K, Yoshitomi H, Tanida S, et al. Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis Res Ther 2010; 12(3): R86.
[http://dx.doi.org/10.1186/ar3013] [PMID: 20470394]
Kolhe R, Hunter M, Liu S, et al. Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis. Sci Rep 2017; 7(1): 2029.
[http://dx.doi.org/10.1038/s41598-017-01905-y] [PMID: 28515465]
Dai L, Zhang X, Hu X, Zhou C, Ao Y. Silencing of microRNA-101 prevents IL-1β-induced extracellular matrix degradation in chondrocytes. Arthritis Res Ther 2012; 14(6): R268.
[http://dx.doi.org/10.1186/ar4114] [PMID: 23227940]
Chen L, Li Q, Wang J, et al. MiR-29b-3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN. J Cell Mol Med 2017; 21(12): 3347-59.
[http://dx.doi.org/10.1111/jcmm.13237] [PMID: 28609022]
Zhao C, Wang Y, Jin H, Yu T. Knockdown of microRNA-203 alleviates LPS-induced injury by targeting MCL-1 in C28/I2 chondrocytes. Exp Cell Res 2017; 359(1): 171-8.
[http://dx.doi.org/10.1016/j.yexcr.2017.07.034] [PMID: 28764893]
Woods S, Barter MJ, Elliott HR, et al. miR-324-5p is up regulated in end-stage osteoarthritis and regulates Indian Hedgehog signalling by differing mechanisms in human and mouse. Matrix Biol 2019; 77: 87-100.
[PMID: 30193893]
Zhang W, Cheng P, Hu W, et al. Downregulated microRNA-340-5p promotes proliferation and inhibits apoptosis of chondrocytes in osteoarthritis mice through inhibiting the extracellular signal-regulated kinase signaling pathway by negatively targeting the FMOD gene. J Cell Physiol 2018; 234(1): 927-39.
[http://dx.doi.org/10.1002/jcp.26921] [PMID: 30144066]
Lin Z, Tian XY, Huang XX, He LL, Xu F. microRNA-186 inhibition of PI3K-AKT pathway via SPP1 inhibits chondrocyte apoptosis in mice with osteoarthritis. J Cell Physiol 2019; 234(5): 6042-53.
[http://dx.doi.org/10.1002/jcp.27225] [PMID: 30500068]
Zhang W, Xia W, Lv Z, Ni C, Xin Y, Yang L. Liquid biopsy for cancer: circulating tumor cells, circulating free DNA or exosomes? Cell Physiol Biochem 2017; 41(2): 755-68.
[http://dx.doi.org/10.1159/000458736] [PMID: 28214887]
Barile L, Vassalli G. Exosomes: therapy delivery tools and biomarkers of diseases. Pharmacol Ther 2017; 174: 63-78.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.020] [PMID: 28202367]
Song J, Kim D, Han J, Kim Y, Lee M, Jin EJ. PBMC and exosome-derived Hotair is a critical regulator and potent marker for rheumatoid arthritis. Clin Exp Med 2015; 15(1): 121-6.
[http://dx.doi.org/10.1007/s10238-013-0271-4] [PMID: 24722995]
Parizadeh SM, Jafarzadeh-Esfehani R, Ghandehari M, et al. Circulating exosomes as potential biomarkers in cardiovascular disease. Curr Pharm Des 2018; 24(37): 4436-44.
[http://dx.doi.org/10.2174/1381612825666181219162655] [PMID: 30569849]
Hosseini M, Khatamianfar S, Hassanian SM, et al. Exosome-encapsulated micrornas as potential circulating biomarkers in colon cancer. Curr Pharm Des 2017; 23(11): 1705-9.
[http://dx.doi.org/10.2174/1381612822666161201144634] [PMID: 27908272]
Hon KW, Abu N, Ab Mutalib NS, Jamal R. Exosomes as potential biomarkers and targeted therapy in colorectal cancer: a mini-review. Front Pharmacol 2017; 8: 583.
[http://dx.doi.org/10.3389/fphar.2017.00583] [PMID: 28894420]
Einhorn TA, Gerstenfeld LC. Fracture healing: mechanisms and interventions. Nat Rev Rheumatol 2015; 11(1): 45-54.
[http://dx.doi.org/10.1038/nrrheum.2014.164] [PMID: 25266456]
Marsell R, Einhorn TA. The biology of fracture healing. Injury 2011; 42(6): 551-5.
[http://dx.doi.org/10.1016/j.injury.2011.03.031] [PMID: 21489527]
Poniatowski LA, Wojdasiewicz P, Gasik R, Szukiewicz D. Transforming growth factor Beta family: insight into the role of growth factors in regulation of fracture healing biology and potential clinical applications. Mediators Inflamm 2015; 2015 137823
[http://dx.doi.org/10.1155/2015/137823] [PMID: 25709154]
Gerstenfeld LC, Cho TJ, Kon T, et al. Impaired fracture healing in the absence of TNF-alpha signaling: the role of TNF-alpha in endochondral cartilage resorption. J Bone Miner Res 2003; 18(9): 1584-92.
[http://dx.doi.org/10.1359/jbmr.2003.18.9.1584] [PMID: 12968667]
Fischer V, Kalbitz M, Müller-Graf F, et al. Influence of menopause on inflammatory cytokines during murine and human bone fracture healing. Int J Mol Sci 2018; 19(7): 19.
[http://dx.doi.org/10.3390/ijms19072070] [PMID: 30013010]
Zhou X, von der Mark K, Henry S, Norton W, Adams H, de Crombrugghe B. Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice. PLoS Genet 2014; 10(12) e1004820
[http://dx.doi.org/10.1371/journal.pgen.1004820] [PMID: 25474590]
Bahney CS, Zondervan RL, Allison P, et al. Cellular biology of fracture healing. J Orthop Res 2019; 37(1): 35-50.
[http://dx.doi.org/10.1002/jor.24170] [PMID: 30370699]
Weilner S, Skalicky S, Salzer B, et al. Differentially circulating miRNAs after recent osteoporotic fractures can influence osteogenic differentiation. Bone 2015; 79: 43-51.
[http://dx.doi.org/10.1016/j.bone.2015.05.027] [PMID: 26026730]
Xu JF, Yang GH, Pan XH, et al. Altered microRNA expression profile in exosomes during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. PLoS One 2014; 9(12) e114627
[http://dx.doi.org/10.1371/journal.pone.0114627] [PMID: 25503309]
Kocijan R, Muschitz C, Geiger E, et al. Circulating microRNA signatures in patients with idiopathic and postmenopausal osteoporosis and fragility fractures. J Clin Endocrinol Metab 2016; 101(11): 4125-34.
[http://dx.doi.org/10.1210/jc.2016-2365] [PMID: 27552543]
Zhang J, Liu X, Li H, et al. Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway. Stem Cell Res Ther 2016; 7(1): 136.
[http://dx.doi.org/10.1186/s13287-016-0391-3] [PMID: 27650895]
Liu L, Liu Y, Feng C, et al. Lithium-containing biomaterials stimulate bone marrow stromal cell-derived exosomal miR-130a secretion to promote angiogenesis. Biomaterials 2019; 192: 523-36.
[http://dx.doi.org/10.1016/j.biomaterials.2018.11.007] [PMID: 30529871]
Li W, Liu Y, Zhang P, et al. Tissue-engineered bone immobilized with human adipose stem cells-derived exosomes promotes bone regeneration. ACS Appl Mater Interfaces 2018; 10(6): 5240-54.
[http://dx.doi.org/10.1021/acsami.7b17620] [PMID: 29359912]
Wei F, Li M, Crawford R, Zhou Y, Xiao Y. Exosome-integrated titanium oxide nanotubes for targeted bone regeneration. Acta Biomater 2019; 86: 480-92.
[http://dx.doi.org/10.1016/j.actbio.2019.01.006] [PMID: 30630122]
Jiang X, Lew KS, Chen Q, Richards AM, Wang P. Human mesenchymal stem cell-derived exosomes reduce ischemia/reperfusion injury by the inhibitions of apoptosis and autophagy. Curr Pharm Des 2018; 24(44): 5334-41.
[http://dx.doi.org/10.2174/1381612825666190119130441] [PMID: 30659531]
Narayanan R, Huang CC, Ravindran S. Hijacking the cellular mail: exosome mediated differentiation of mesenchymal stem cells. Stem Cells Int 2016; 2016 3808674
[http://dx.doi.org/10.1155/2016/3808674] [PMID: 26880957]
Furuta T, Miyaki S, Ishitobi H, et al. Mesenchymal stem cell-derived exosomes promote fracture healing in a mouse model. Stem Cells Transl Med 2016; 5(12): 1620-30.
[http://dx.doi.org/10.5966/sctm.2015-0285] [PMID: 27460850]
Stegen S, van Gastel N, Carmeliet G. Bringing new life to damaged bone: the importance of angiogenesis in bone repair and regeneration. Bone 2015; 70: 19-27.
[http://dx.doi.org/10.1016/j.bone.2014.09.017] [PMID: 25263520]
Jia Y, Zhu Y, Qiu S, Xu J, Chai Y. Exosomes secreted by endothelial progenitor cells accelerate bone regeneration during distraction osteogenesis by stimulating angiogenesis. Stem Cell Res Ther 2019; 10(1): 12.
[http://dx.doi.org/10.1186/s13287-018-1115-7] [PMID: 30635031]
Zhang Y, Hao Z, Wang P, et al. Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1α-mediated promotion of angiogenesis in a rat model of stabilized fracture. Cell Prolif 2019; 52(2) e12570
[http://dx.doi.org/10.1111/cpr.12570] [PMID: 30663158]
Wu F, Li F, Lin X, et al. Exosomes increased angiogenesis in papillary thyroid cancer microenvironment. Endocr Relat Cancer 2019. pii: ERC-19-0008.R1.
[http://dx.doi.org/10.1530/ERC-19-0008] [PMID: 30870812]
Chen Y, Xue K, Zhang X, Zheng Z, Liu K. Exosomes derived from mature chondrocytes facilitate subcutaneous stable ectopic chondrogenesis of cartilage progenitor cells. Stem Cell Res Ther 2018; 9(1): 318.
[http://dx.doi.org/10.1186/s13287-018-1047-2] [PMID: 30463592]
Li R, Chen C, Zheng RQ, Zou L, Hao GL, Zhang GC. Influences of hucMSC-exosomes on VEGF and BMP-2 expression in SNFH rats. Eur Rev Med Pharmacol Sci 2019; 23(7): 2935-43.
[PMID: 31002144]
Kordelas L, Rebmann V, Ludwig AK, et al. MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease. Leukemia 2014; 28(4): 970-3.
[http://dx.doi.org/10.1038/leu.2014.41] [PMID: 24445866]
Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 2013; 200(4): 373-83.
[http://dx.doi.org/10.1083/jcb.201211138] [PMID: 23420871]
Li T, Yan Y, Wang B, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev 2013; 22(6): 845-54.
[http://dx.doi.org/10.1089/scd.2012.0395] [PMID: 23002959]
Doeppner TR, Herz J, Görgens A, et al. Extracellular vesicles improve post-stroke neuroregeneration and prevent postischemic immunosuppression. Stem Cells Transl Med 2015; 4(10): 1131-43.
[http://dx.doi.org/10.5966/sctm.2015-0078] [PMID: 26339036]
Couzin J. Cell biology: the ins and outs of exosomes. Science 2005; 308(5730): 1862-3.
[http://dx.doi.org/10.1126/science.308.5730.1862] [PMID: 15976285]
Lobb RJ, Becker M, Wen SW, et al. Optimized exosome isolation protocol for cell culture supernatant and human plasma. J Extracell Vesicles 2015; 4: 27031.
[http://dx.doi.org/10.3402/jev.v4.27031] [PMID: 26194179]
Lötvall J, Hill AF, Hochberg F, et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles 2014; 3: 26913.
[http://dx.doi.org/10.3402/jev.v3.26913] [PMID: 25536934]
Morishita M, Takahashi Y, Nishikawa M, et al. Quantitative analysis of tissue distribution of the B16BL6-derived exosomes using a streptavidin-lactadherin fusion protein and iodine-125-labeled biotin derivative after intravenous injection in mice. J Pharm Sci 2015; 104(2): 705-13.
[http://dx.doi.org/10.1002/jps.24251] [PMID: 25393546]
Gimona M, Pachler K, Laner-Plamberger S, Schallmoser K, Rohde E. Manufacturing of human extracellular vesicle-based therapeutics for clinical use. Int J Mol Sci 2017; 18(6): 18.
[http://dx.doi.org/10.3390/ijms18061190] [PMID: 28587212]

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Year: 2019
Published on: 07 January, 2020
Page: [4536 - 4549]
Pages: 14
DOI: 10.2174/1381612825666191127114054
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