| First Author | Yang JI | Year | 2021 |
| Journal | Arthritis Res Ther | Volume | 23 |
| Issue | 1 | Pages | 114 |
| PubMed ID | 33853646 | Mgi Jnum | J:309619 |
| Mgi Id | MGI:6758865 | Doi | 10.1186/s13075-021-02485-z |
| Citation | Yang JI, et al. (2021) Upregulated endonuclease Regnase-1 suppresses osteoarthritis by forming a negative feedback loop of catabolic signaling in chondrocytes. Arthritis Res Ther 23(1):114 |
| abstractText | BACKGROUND: Ribonucleases (RNases) play central roles in the post-transcriptional regulation of mRNA stability. Our preliminary results revealed that the endonuclease Regnase-1 is specifically upregulated in osteoarthritic chondrocytes. We herein explored the possible functions and regulatory mechanisms of Regnase-1 in a mouse model of osteoarthritis (OA). METHODS: The expression and target genes of Regnase-1 were identified by microarray analysis in primary-culture mouse articular chondrocytes. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM). The function of Regnase-1 in DMM-induced post-traumatic OA mice was examined by adenovirus-mediated overexpression or knockdown in knee joint tissues, and also by using Regnase-1 heterozygous knockout mice (Zc3h12a(+/-)). RESULTS: Among the RNases, Regnase-1 was exclusively upregulated in chondrocytes stimulated with OA-associated catabolic factors. Adenovirus-mediated overexpression or knockdown of Regnase-1 alone in joint tissues did not cause OA-like changes. However, overexpression of Regnase-1 in joint tissues significantly ameliorated DMM-induced post-traumatic OA cartilage destruction, whereas knockdown or genetic ablation of Regnase-1 exacerbated DMM-induced cartilage destruction. Mechanistic studies suggested that Regnase-1 suppresses cartilage destruction by modulating the expression of matrix-degrading enzymes in chondrocytes. CONCLUSION: Our results collectively suggest that upregulated Regnase-1 in OA chondrocytes may function as a chondro-protective effector molecule during OA pathogenesis by forming a negative feedback loop of catabolic signals, such as matrix-degrading enzyme expression, in OA chondrocytes. |
