Epigenetic regulation of chondrocyte hypertrophy and apoptosis through Sirt1/P53/P21 pathway in surgery-induced osteoarthritis.

Sirt1 involved in cellular aging and aging-related diseases, including osteoarthritis (OA). Our previous study showed Sirt1 played a role in the pathogenesis of OA, however, the underlying mechanisms are still poorly elicited. In this study, we investigated the role of Sirt1 in epigenetically regulating P53/P21 pathway in a Sirt1 loss model. Sirt1 deletion male mice (n = 10) with destabilization of the medial meniscus (DMM) were used to observe its role on OA development. Then, the relationships between SIRT1 and P53 were detected by Coimmunoprecipitation (CoIP), and the gain-off function of P53 gene was indicated by P53 activators and inhibitors in vitro. Finally, human cartilage samples from patients with OA were collected. Sirt1 deletion mice displayed a spontaneous OA development, manifesting severe chondrocytes hypertrophy markers MMP13 and ADAMTS5, highly expressed P53 and P21. Strikingly, surgery-induced meniscus injury promoted the OA pathogenesis and apoptosis in Sirt1 deficient mice. Ultimately, our CoIP data demonstrated that Sirt1 directly interacted with P53 in vitro. However inhibition of P53 alleviated OA progression. We also observed that chondrocyte apoptosis and P53 increased in osteoarthritis (OA) progression with a declining expression of Sirt1 in human cartilage. Loss of Sirt1 in cartilage led to accelerated OA pathogenesis via aberrant activation of p53/p21 mediated senescence associated secretory phenotype, hypertrophy and apoptosis.

Xu M ，Feng M ，Peng H ，Qian Z ，Zhao L ，Wu S ... -  《-》

MicroRNA-34a affects chondrocyte apoptosis and proliferation by targeting the SIRT1/p53 signaling pathway during the pathogenesis of osteoarthritis.

Yan S ，Wang M ，Zhao J ，Zhang H ，Zhou C ，Jin L ，Zhang Y ，Qiu X ，Ma B ，Fan Q ... -  《-》

Leptin changes differentiation fate and induces senescence in chondrogenic progenitor cells.

Zhao X ，Dong Y ，Zhang J ，Li D ，Hu G ，Yao J ，Li Y ，Huang P ，Zhang M ，Zhang J ，Huang Z ，Zhang Y ，Miao Y ，Xu Q ，Li H ... -  《-》

SirT1 enhances survival of human osteoarthritic chondrocytes by repressing protein tyrosine phosphatase 1B and activating the insulin-like growth factor receptor pathway.

Gagarina V ，Gabay O ，Dvir-Ginzberg M ，Lee EJ ，Brady JK ，Quon MJ ，Hall DJ ... -  《-》

[Mechanism of Huangqin Qingre Chubi Capsules regulating p53/p21 signaling pathway to delay chondrocyte senescence in osteoarthritic rats].

Zhou Q ，Liu J ，Zhu Y ，Wang Y ，Wang GZ ，Wan L ，Huang D ，Guo JC ，Qi YJ ，Hu YD ... -  《-》