miR-223 promotes cartilage differentiation of bone marrow-derived mesenchymal stem cells and protects against osteoarthritis by suppressing NLRP-3 expression
Nan Min 1,   Jie Ma 2,   Lei Shi 1,   Lin Wang 1,   Chi Liu 1,   Yaonan Zhang 1,   Qingyun Xue 1
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Department of Orthopedics, Beijing Hospital, Beijing, China
Center of Biotherapy, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
Submission date: 2020-08-03
Final revision date: 2020-09-03
Acceptance date: 2020-09-05
Online publication date: 2020-11-06
The present investigation evaluates the role of miR-223 mimic in the treatment of osteoarthritis (OA) and postulates the possible molecular mechanism of its action.

Material and methods:
Bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from rats and cultured in chondrogenic medium to stimulate the differentiation of chondrocytes. Alcian blue staining was performed to determine the chondrogenic differentiation and expression of miR-223 in the BMSCs. Moreover, expression of NLR family pyrin domain containing 3 (NLRP-3), matrix metallopeptidase-13 (MMP-13) and collagen (Col II) was determined in miR-223 mimic and inhibitor treated BMSCs. OA was induced by injecting anterior cruciate ligament transection in rats followed by further treatment with the miR-223 mimic for the period of the treatment protocol. Level and expression of inflammatory cytokines were estimated in the cartilage tissue of OA rats. Moreover, immunohistochemical analysis and histopathology study were also performed.

Data of the study reveal that expression of miR-223 was higher in chondrogenic differentiated BMSCs than normal. Expression of MMP-13 and NLRP-3 was lower, and expression of Col II was higher in miR-223 mimic treated BMSCs than normal. Moreover, data of the in-vivo study indicate that the expression level of cytokines was lower in the cartilage tissue of the miR-223 mimic treated group than the OA group. Treatment with the miR-223 mimic ameliorates the altered histopathology and expression of NLRP-3 in the cartilage tissue of OA rats.

Data of the study reveal that the miR-223 mimic enhances the chondrogenic differentiation of BMSCs by regulating the NLRP-3/IL-18/TGF-b pathway.