| First Author | Zhang Y | Year | 2024 |
| Journal | Int J Biol Sci | Volume | 20 |
| Issue | 6 | Pages | 1965-1977 |
| PubMed ID | 38617544 | Mgi Jnum | J:352335 |
| Mgi Id | MGI:7622453 | Doi | 10.7150/ijbs.90250 |
| Citation | Zhang Y, et al. (2024) Deficiency of Cbfbeta in articular cartilage leads to osteoarthritis-like phenotype through Hippo/Yap, TGFbeta, and Wnt/beta-catenin signaling pathways. Int J Biol Sci 20(6):1965-1977 |
| abstractText | Osteoarthritis (OA) is the most prevalent degenerative joint disorder, causing physical impairments among the elderly. Core binding factor subunit beta (Cbfbeta) has a critical role in bone homeostasis and cartilage development. However, the function and mechanism of Cbfbeta in articular cartilage and OA remains unclear. We found that Cbfbeta(f/f)Aggrecan-CreER(T) mice with Cbfbeta-deficiency in articular cartilage developed a spontaneous osteoarthritis-like phenotype with articular cartilage degradation. Immunofluorescence staining showed that Cbfbeta(f/f)Aggrecan-CreER(T) mice exhibited a significant increase in the expression of articular cartilage degradation markers and inflammatory markers in the knee joints. RNA-sequencing analysis demonstrated that Cbfbeta orchestrated Hippo/Yap, TGFbeta/Smad, and Wnt/beta-catenin signaling pathways in articular cartilage, and Cbfbeta deficiency resulted in the abnormal expression of downstream genes involved in maintaining articular cartilage homeostasis. Immunofluorescence staining results showed Cbfbeta deficiency significantly increased active beta-catenin and TCF4 expression while reducing Yap, TGFbeta1, and p-Smad 2/3 expression. Western blot and qPCR validated gene expression changes in hip articular cartilage of Cbfbeta-deficient mice. Our results demonstrate that deficiency of Cbfbeta in articular cartilage leads to an OA-like phenotype via affecting Hippo/Yap, TGFbeta, and Wnt/beta-catenin signaling pathways, disrupting articular cartilage homeostasis and leading to the pathological process of OA in mice. Our results indicate that targeting Cbfbeta may be a potential therapeutic target for the design of novel and effective treatments for OA. |
