Abstract
Background:
Stem cells intra-articular injection stagey indicated a potential therapeutic effect on improving the pathological progress of osteoarthritis (OA). However, the long-term effect of stem cells intra-articular injection on the cartilage regeneration remains unclear. miR-29a-3p is predicted to be a critical target for inhibiting insulin-like growth factor-1 expression and may aggravate the progression of OA.
Methods:
In this study, we investigated the therapeutic efficacy of intra-articular injection of bone marrow mesenchymal stem cells (BMSCs) transfected with miR-29a-3p inhibitor in OA.
Results:
miR-29a-3p inhibitor transfection did not influence cell viability of BMSCs, while the chondrogenic differentiation potential of BMSCs was significantly improved. Interestingly, intra-articular injection of BMSCs with miR-29a-3p inhibition significantly prevented articular cartilage degeneration by up-regulating the expression of Sox 9, Col-2a1, aggrecan and down-regulating the expression of matrix metalloproteinase, as well as relieved pain in OA.
Conclusion:
The double effects on cartilage protection and pain relief indicated a great potential of intra-articular injection of miR-29a-3p inhibitor-transfected BMSCs for the treatment of OA.
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References
Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003;48:3464–74.
Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted. Pain Physician. 2008;11:343–53.
Csaki C, Schneider PR, Shakibaei M. Mesenchymal stem cells as a potential pool for cartilage tissue engineering. Ann Anat. 2008;190:395–412.
Maumus M, Guérit D, Toupet K, Jorgensen C, Noël D. Mesenchymal stem cell-based therapies in regenerative medicine: applications in rheumatology. Stem Cell Res Ther. 2011;2:14.
Barry F, Murphy M. Mesenchymal stem cells in joint disease and repair. Nat Rev Rheumatol. 2013;9:584–94.
Bertoni L, Jacquet-Guibon S, Branly T, Desancé M,, Legendre F, Melin M, et al. Evaluation of allogeneic bone-marrow-derived and umbilical cord blood-derived mesenchymal stem cells to prevent the development of osteoarthritis in an equine model. Int J Mol Sci. 2021;22:2499.
Hwang JJ, Rim YA, Nam Y, Ju JH. Recent developments in clinical applications of mesenchymal stem cells in the treatment of rheumatoid arthritis and osteoarthritis. Front Immunol. 2021;12:631291.
Koga H, Shimaya M, Muneta T, Nimura A, Morito T, Hayashi M, et al. Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Res Ther. 2008;10:R84.
Chang YH, Liu HW, Wu KC, Ding DC. Mesenchymal stem cells and their clinical applications in osteoarthritis. Cell Transplant. 2016;25:937–50.
Ha CW, Park YB, Kim SH, Lee HJ. Intra-articular mesenchymal stem cells in osteoarthritis of the knee: a systematic review of clinical outcomes and evidence of cartilage repair. Arthroscopy. 2019;35:277–88.e2.
Freyria AM, Mallein-Gerin F. Chondrocytes or adult stem cells for cartilage repair: the indisputable role of growth factors. Injury. 2012;43:259–65.
Hussen BM, Hidayat HJ, Salihi A, Sabir DK, Taheri M, Ghafouri-Fard S. MicroRNA: a signature for cancer progression. Biomed Pharmacother. 2021;138:111528.
Kao GS, Tu YK, Sung PH, Wang FS, Lu YD, Wu CT, et al. MicroRNA-mediated interacting circuits predict hypoxia and inhibited osteogenesis of stem cells, and dysregulated angiogenesis are involved in osteonecrosis of the femoral head. Int Orthop. 2018;42:1605–14.
Yao C, Wu W, Tang H, Jia X, Tang J, Ruan X, et al. Self-assembly of stem cell membrane-camouflaged nanocomplex for microRNA-mediated repair of myocardial infarction injury. Biomaterials 2020;257:120256.
Geng Y, Chen J, Alahdal M, Chang C, Duan L, Zhu W, et al. Intra-articular injection of hUC-MSCs expressing miR-140-5p induces cartilage self-repairing in the rat osteoarthritis. J Bone Miner Metab. 2020;38:277–88.
Bai H, Zhao Y, Wang C, Wang Z, Wang J, Liu H, et al. Enhanced osseointegration of three-dimensional supramolecular bioactive interface through osteoporotic microenvironment regulation. Theranostics. 2020;10:4779–94.
Glasson SS, Blanchet TJ, Morris EA. The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse. Osteoarthritis Cartilage. 2007;15:1061–9.
Shao Y, Zhao C, Pan J, Zeng C, Zhang H, Liu L, et al. BMP5 silencing inhibits chondrocyte senescence and apoptosis as well as osteoarthritis progression in mice. Aging (Albany NY). 2021;13:9646–64.
Kang ML, Jeong SY, Im GI. Hyaluronic acid hydrogel functionalized with self-assembled micelles of amphiphilic PEGylated kartogenin for the treatment of osteoarthritis. Tissue Eng Part A. 2017;23:630–9.
Micheli L, Bozdag M, Akgul O, Carta F, Guccione C, Bergonzi MC, et al. Pain relieving effect of-NSAIDs-CAIs hybrid molecules: systemic and intra-articular treatments against rheumatoid arthritis. Int J Mol Sci. 2019;20:1923.
Peng XB, Zhang Y, Wang YQ, He Q, Yu Q. IGF-1 and BMP-7 synergistically stimulate articular cartilage repairing in the rabbit knees by improving chondrogenic differentiation of bone-marrow mesenchymal stem cells. J Cell Biochem. 2019;120:5570–82.
Qasim M, Le NXT, Nguyen TPT, Chae DS, Park SJ, Lee NY. Nanohybrid biodegradable scaffolds for TGF-beta 3 release for the chondrogenic differentiation of human mesenchymal stem cells. Int J Pharm. 2020;581:119248.
Taghavi M, Parham A, Raji A. The combination of TGF-beta 3 and BMP-6 synergistically promotes the chondrogenic differentiation of equine bone marrow-derived mesenchymal stem cells. Int J Pept Res Ther. 2020;26:727–35.
Ruiz M, Maumus M, Fonteneau G, Pers YM, Ferreira R, Dagneaux L, et al. TGF beta i is involved in the chondrogenic differentiation of mesenchymal stem cells and is dysregulated in osteoarthritis. Osteoarthritis Cartilage. 2019;27:493–503.
Mueller MB, Fischer M, Zellner J, Berner A, Dienstknecht T, Prantl L, et al. Hypertrophy in mesenchymal stem cell chondrogenesis: effect of tgf-beta isoforms and chondrogenic conditioning. Cells Tissues Organs. 2010;192:158–66.
Mara CS, Duarte AS, Sartori A, Luzo AC, Saad ST, Coimbra IB. Regulation of chondrogenesis by transforming growth factor-beta 3 and insulin-like growth factor-1 from human mesenchymal umbilical cord blood cells. J Rheumatol. 2010;37:1519–26.
Kwon JY, Lee SH, Na HS, Jung K, Choi J, Cho KH, et al. Kartogenin inhibits pain behavior, chondrocyte inflammation, and attenuates osteoarthritis progression in mice through induction of IL-10. Sci Rep. 2018;8:13832.
Hu Q, Ecker M. Overview of MMP-13 as a promising target for the treatment of osteoarthritis. Int J Mol Sci. 2021;22:1742.
Lan Q, Lu R, Chen H, Pang Y, Xiong F, Shen C, et al. MMP-13 enzyme and pH responsive theranostic nanoplatform for osteoarthritis. J Nanobiotechnology. 2020;18:117.
Nazempour A, Van Wie BJ. Chondrocytes, mesenchymal stem cells, and their combination in articular cartilage regenerative medicine. Ann Biomed Eng. 2016;44:1325–54.
Boyden SD, Hossain IN, Wohlfahrt A, Lee YC. Non-inflammatory causes of pain in patients with rheumatoid arthritis. Curr Rheumatol Rep. 2016;18:30.
Meeus M, Vervisch S, De Clerck LS, Moorkens G, Hans G, Nijs J. Central sensitization in patients with rheumatoid arthritis: a systematic literature review. Semin Arthritis Rheum. 2012;41:556–67.
Zhang A, Lee YC. Mechanisms for joint pain in rheumatoid arthritis (RA): from cytokines to central sensitization. Curr Osteoporos Rep. 2018;16:03–610.
Pinho-Ribeiro FA, Verri WA Jr, Chiu IM. Nociceptor sensory neuron-immune interactions in pain and inflammation. Trends Immunol. 2017;38:5–19.
Acknowledgement
This study has been supported by Suzhou People's Livelihood Science and Technology (Project No. SYS2020065).
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All animal procedures were performed in accordance with the guidelines for Care and Use of Laboratory Animal Experience and approved by the Animal Care and Use Ethics Committee of Nanjing University of Chinese Medicine (no. ACU191101).
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Wang, Q., Chen, Y., Shen, X. et al. Intra-Articular Injection of miR-29a-3p of BMSCs Promotes Cartilage Self-Repairing and Alleviates Pain in the Rat Osteoarthritis. Tissue Eng Regen Med 18, 1045–1055 (2021). https://doi.org/10.1007/s13770-021-00384-7
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DOI: https://doi.org/10.1007/s13770-021-00384-7