Shao Yan, Zhao Chang, Pan Jianying, Zeng Chun, Zhang Hongbo, Liu Liangliang, Fan Kai, Liu Xin, Luo Bingsheng, Fang Hang, Bai Xiaochun, Zhang Haiyan, Cai Daozhang
Department of Orthopedics, Orthopedic Hospital of Guangdong Province, Academy of Orthopedics Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Aging (Albany NY). 2021 Mar 19;13(7):9646-9664. doi: 10.18632/aging.202708.
In this study, we using the destabilization of the medial meniscus (DMM) mouse model to investigate the role of bone morphogenetic protein 5 (BMP5) in osteoarthritis (OA) progression mediated via chondrocyte senescence and apoptosis. BMP5 expression was significantly higher in knee articular cartilage tissues of OA patients and DMM model mice than the corresponding controls. The Osteoarthritis Research Society International scores based on histological staining of knee articular cartilage sections were lower in DMM mice where BMP5 was knocked down in chondrocytes than the corresponding controls 4 weeks after DMM surgery. DMM mice with BMP5-deficient chondrocytes showed reduced levels of matrix-degrading enzymes such as MMP13 and ADAMTS5 as well as reduced cartilage destruction. BMP5 knockdown also decreased chondrocyte apoptosis and senescence by suppressing the activation of p38 and ERK MAP kinases. These findings demonstrate that BMP5 silencing inhibits chondrocyte senescence and apoptosis as well as OA progression by downregulating activity in the p38/ERK signaling pathway.
在本研究中，我们使用内侧半月板不稳定（DMM）小鼠模型来研究骨形态发生蛋白5（BMP5）在通过软骨细胞衰老和凋亡介导的骨关节炎（OA）进展中的作用。OA患者和DMM模型小鼠的膝关节软骨组织中BMP5表达明显高于相应对照组。在DMM手术后4周，软骨细胞中BMP5被敲低的DMM小鼠基于膝关节软骨切片组织学染色的国际骨关节炎研究学会评分低于相应对照组。软骨细胞缺乏BMP5的DMM小鼠显示出基质降解酶如MMP13和ADAMTS5水平降低以及软骨破坏减少。BMP5敲低还通过抑制p38和ERK丝裂原活化蛋白激酶的激活来减少软骨细胞凋亡和衰老。这些发现表明，BMP5沉默通过下调p38/ERK信号通路的活性来抑制软骨细胞衰老和凋亡以及OA进展。
