RRC ID 70504
著者 Ruiz-Fernández C, González-Rodríguez M, Abella V, Francisco V, Cordero-Barreal A, Ait Eldjoudi D, Farrag Y, Pino J, Conde-Aranda J, González-Gay MÁ, Mera A, Mobasheri A, García-Caballero L, Gándara-Cortés M, Lago F, Scotece M, Gualillo O.
タイトル WISP-2 modulates the induction of inflammatory mediators and cartilage catabolism in chondrocytes.
ジャーナル Lab Invest
Abstract Wnt-1 inducible signaling pathway protein 2 (WISP-2/CCN5) is a recently identified adipokine that has been described as an important mediator of canonical Wnt activation in adipogenic precursor cells. In osteoarthritis (OA), the most common form of arthritis, chondrocytes exhibit aberrant and increased production of pro-inflammatory mediators and matrix degrading enzymes such as IL-1β and MMP-13. Although recent evidence suggests a role for Wnt signaling in OA physiopathology, little is known about the involvement of WISP-2 in cartilage degradation. In the present study, we determined the expression of WISP-2 in healthy and OA human chondrocytes. WISP-2 expression is modulated along chondrocyte differentiation and downregulated at the onset of hypertrophy by inflammatory mediators. We also investigated the effect of WISP-2 on cartilage catabolism and performed WISP-2 loss-of-function experiments using RNA interference technology in human T/C-28a2 immortalized chondrocytes. We demonstrated that recombinant human WISP-2 protein reduced IL-1β-mediated chondrocyte catabolism, that IL-1β and WNT/b-catenin signaling pathways are involved in rhWISP-2 protein and IL-1β effects in human chondrocytes, and that WISP-2 has a regulatory role in attenuating the catabolic effects of IL-1β in chondrocytes. Gene silencing of WISP-2 increased the induction of the catabolic markers MMP-13 and ADAMTS-5 and the inflammatory mediators IL-6 and IL-8 triggered by IL-1β in human primary OA chondrocytes in a Wnt/β-catenin dependent manner. In conclusion, here we have shown for the first time that WISP-2 may have relevant roles in modulating the turnover of extracellular matrix in the cartilage and that its downregulation may detrimentally alter the inflammatory environment in OA cartilage. We also proved the participation of Wnt/β-catenin signaling pathway in these processes. Thus, targeting WISP-2 might represent a potential therapeutical approach for degenerative and/or inflammatory diseases of musculoskeletal system, such as osteoarthritis.
巻・号 102(9)
ページ 989-999
公開日 2022-9-1
DOI 10.1038/s41374-022-00793-9
PII 10.1038/s41374-022-00793-9
PMID 35484291
MeSH CCN Intercellular Signaling Proteins Cartilage Cells, Cultured Chondrocytes* Humans Inflammation Mediators Interleukin-1beta Matrix Metalloproteinase 13 Osteoarthritis* Repressor Proteins Wnt Signaling Pathway
IF 4.197
リソース情報
ヒト・動物細胞 ATDC5(RCB0565)