G protein coupled estrogen receptor attenuates mechanical stress-mediated apoptosis of chondrocyte in osteoarthritis via suppression of Piezo1

• DOI: 10.1186/s10020-021-00360-w
• Publication Date: 2021-08-28T12:02:54Z
• Authors: Yi Sun; Ping Leng; Pengcheng Guo; Huanshen Gao; Yikai Liu; Chenkai Li; Zhenghui Li; Haining Zhang
• Keywords: GPER

Apoptosis of chondrocyte is involved in osteoarthritis (OA) pathogenesis, and mechanical stress plays a key role this process by activation Piezo1. However, the negative regulation signal conduction mediated still unclear. Here, we elucidate that critical G protein coupled estrogen receptor (GPER) stress-mediated transduction apoptosis.The gene expression profile was detected chip upon silencing The GPER cartilage tissue taken from clinical patients RT-PCR Western blot as well immunohistochemistry, correlation between OA also investigated. chondrocytes exposed to were treated with estrogen, G-1, G15, GPER-siRNA YAP (Yes-associated protein)-siRNA. cell viability measured. polymerized actin Piezo1 subcellular localization observed under laser confocal microscope. confirmed changes YAP/ Rho GTPase activating 29 (ARHGAP29) /RhoA/LIMK /Cofilin pathway. knee specimens model stained safranin green. OARSI score used evaluate joint lesions. expressions immunochemistry.Expression profiles Piezo1- silenced showed significantly upregulated. Moreover, negatively correlated degeneration during pathogenesis. In addition, uncovered directly targeted broadly restrained stress-triggered polymerization. Mechanism studies revealed inhibited RhoA/LIMK/cofilin pathway, polymerization, promoting ARHGAP29, nuclear localization, eventually causing inhibition obviously decreased degenerated cartilage. Silencing caused increased polymerization Piezo1, an increase apoptosis. intra-articular injection G-1 rat effectively attenuated degeneration.We propose novel regulatory mechanism underlying apoptosis potential application value therapy targets for OA.