PMID- 31760502 OWN - NLM STAT- MEDLINE DCOM- 20200625 LR - 20210110 IS - 1435-5604 (Electronic) IS - 0914-8779 (Linking) VI - 38 IP - 3 DP - 2020 May TI - Intra-articular injection of hUC-MSCs expressing miR-140-5p induces cartilage self-repairing in the rat osteoarthritis. PG - 277-288 LID - 10.1007/s00774-019-01055-3 [doi] AB - INTRODUCTION: Currently, osteoarthritis (OA) receives global increasing attention because it associates severe joint pain and serious disability. Stem cells intra-articular injection therapy showed a potential therapeutic superiority to reduce OA development and to improve treating outputs. However, the long-term effect of stem cells intra-articular injection on the cartilage regeneration remains unclear. Recently, miR-140-5p was confirmed as a critical positive regulator in chondrogenesis. We hypothesized that hUC-MSCs overexpressing miR-140-5p have better therapeutic effect on osteoarthritis. MATERIALS AND METHODS: To enhance stem cell chondrogenic differentiation, we have transfected human umbilical cord mesenchymal stem cells (hUC-MSCs) with miR-140-5p mimics and miR-140-5p lentivirus to overexpress miR-140-5p in a short term or a long term accordingly. Thereafter, MSCs proliferation, chondrogenic genes expression and extracellular matrix were assessed. Destabilization of the medial meniscus (DMM) surgery was performed on the knee joints of SD rats as an OA model, and then intra-articular injection of hUC-MSCs or hUC-MSCs transfected with miR-140-5p lentivirus was carried to evaluate the cartilage healing effect with histological staining and OARSI scores. The localization of hUC-MSCs after intra-articular injection was further confirmed by immunohistochemical staining. RESULTS: Significant induction of chondrogenic differentiation in the miR-140-5p-hUC-MSCs (140-MSCs), while its proliferation was not influenced. Interestingly, intra-articular injection of 140-MSCs significantly enhanced articular cartilage self-repairing in comparison to normal hUC-MSCs. Moreover, we noticed that intra-articular injection of high 140-MSCs numbers reinforces cells assembling on the impaired cartilage surface and subsequently differentiated into chondrocytes. CONCLUSIONS: In conclusion, these results indicate therapeutic superiority of hUC-MSCs overexpressing miR-140-5p to treat OA using intra-articular injection. FAU - Geng, Yiyun AU - Geng Y AD - The First Affiliated Hospital to Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong Province, China. AD - Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen, 518035, Guangdong Province, China. AD - Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518035, Guangdong Province, China. FAU - Chen, Jinfu AU - Chen J AD - The First Affiliated Hospital to Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong Province, China. FAU - Alahdal, Murad AU - Alahdal M AD - The First Affiliated Hospital to Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong Province, China. AD - Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen, 518035, Guangdong Province, China. AD - Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China. FAU - Chang, Chongfei AU - Chang C AD - The First Affiliated Hospital to Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong Province, China. FAU - Duan, Li AU - Duan L AD - The First Affiliated Hospital to Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong Province, China. AD - Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen, 518035, Guangdong Province, China. FAU - Zhu, Weimin AU - Zhu W AD - The First Affiliated Hospital to Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong Province, China. FAU - Mou, Lisha AU - Mou L AD - The First Affiliated Hospital to Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong Province, China. FAU - Xiong, Jianyi AU - Xiong J AD - The First Affiliated Hospital to Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong Province, China. AD - Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen, 518035, Guangdong Province, China. FAU - Wang, Manyi AU - Wang M AD - The First Affiliated Hospital to Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong Province, China. FAU - Wang, Daping AU - Wang D AD - The First Affiliated Hospital to Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, Guangdong Province, China. dapingwang1963@qq.com. AD - Guangdong Provincial Research Center for Artificial Intelligence and Digital Orthopedic Technology, Shenzhen, 518035, Guangdong Province, China. dapingwang1963@qq.com. LA - eng GR - 81572198/National Natural Science Foundation of China/ GR - 81772394/National Natural Science Foundation of China/ GR - 2018B0303110003/Key Program of Natural Science Foundation of Guangdong Province/ GR - KQTD20170331100838136/Shenzhen Peacock Project/ GR - JCYJ20170817172023838/Shenzhen Science and Technology Projects/ GR - JCYJ20170306092215436/Shenzhen Science and Technology Projects/ GR - JCYJ20170412150609690/Shenzhen Science and Technology Projects/ GR - JCYJ20170413161649437/Shenzhen Science and Technology Projects/ GR - JCYJ20170413161800287/Shenzhen Science and Technology Projects/ GR - SGLH20161209105517753/Shenzhen Science and Technology Projects/ GR - JCYJ20160301111338144/Shenzhen Science and Technology Projects/ GR - 2016031638/Fund for High Level Medical Discipline Construction of Shenzhen University/ PT - Journal Article DEP - 20191123 PL - Japan TA - J Bone Miner Metab JT - Journal of bone and mineral metabolism JID - 9436705 RN - 0 (MicroRNAs) RN - 0 (Mirn140 microRNA, human) SB - IM MH - Animals MH - Cartilage, Articular/metabolism/*pathology MH - Cell Differentiation/genetics MH - Chondrocytes/cytology MH - Chondrogenesis MH - Disease Models, Animal MH - Humans MH - Injections, Intra-Articular MH - Lentivirus/metabolism MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology MH - MicroRNAs/*metabolism MH - Osteoarthritis/genetics/*therapy MH - Rats, Sprague-Dawley MH - *Regeneration MH - Umbilical Cord/*cytology OTO - NOTNLM OT - Cartilage OT - Human umbilical cord mesenchymal stem cells OT - Osteoarthritis OT - miR-140-5p EDAT- 2019/11/25 06:00 MHDA- 2020/06/26 06:00 CRDT- 2019/11/25 06:00 PHST- 2019/06/05 00:00 [received] PHST- 2019/10/10 00:00 [accepted] PHST- 2019/11/25 06:00 [pubmed] PHST- 2020/06/26 06:00 [medline] PHST- 2019/11/25 06:00 [entrez] AID - 10.1007/s00774-019-01055-3 [pii] AID - 10.1007/s00774-019-01055-3 [doi] PST - ppublish SO - J Bone Miner Metab. 2020 May;38(3):277-288. doi: 10.1007/s00774-019-01055-3. Epub 2019 Nov 23.