Ezh2 Ameliorates Osteoarthritis by Activating TNFSF13B
Ezh2 Ameliorates Osteoarthritis by Activating TNFSF13B
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Ezh2 通过激活 TNFSF13B 改善骨关节炎
DOI：
10.1002/jbmr.3952
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发表时间：
2020-02-03
影响因子：
6.2
通讯作者：
Ouyang, Hongwei
中科院分区：
文献类型：
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作者：
Du, Xiaotian;Chen, Yishan;Ouyang, Hongwei
表观遗传调控与骨关节炎（OA）的发展高度相关，但其作用和详细机制仍然难以捉摸。在本研究中，我们探讨了 EZH2（一种 H3K27me3 转移酶）在人 OA 软骨中的表达及其在调节 OA 发病机制中的作用。在这里，我们通过组织学分析和 RNA 测序 (RNA-Seq) 发现 EZH2 在小鼠和人类 OA 软骨样本中高表达。内侧半月板切除术 (MMx) OA 模型结果表明，条件性敲除 Ezh2 会恶化 OA 病理状况。此外，我们还发现 Ezh2 通过激活肿瘤坏死因子超家族成员 TNFSF13B 在软骨伤口愈合和抑制肥大中发挥积极作用。此外，我们还指出，Ezh2 增强的 TNFSF13B 的作用可能通过增加 Akt 的磷酸化来促进软骨细胞的愈合。综上所述，我们的结果发现 OA 患者中存在 EZH2 阳性亚群，并且 EZH2-TNFSF13B 信号传导负责调节软骨细胞愈合和肥大。因此，EZH2可能成为OA诊断和治疗的新的潜在靶点。 © 2020 美国骨与矿物质研究学会。
Epigenetic regulation is highly correlated with osteoarthritis (OA) development, whereas its role and detailed mechanisms remain elusive. In this study, we explored the expression of EZH2, an H3K27me3 transferase, in human OA cartilages and its roles in regulating OA pathogenesis. Here, we found EZH2 was highly expressed in both mice and human OA cartilage samples by using histological analysis and RNA sequencing (RNA‐Seq). The medial meniscectomy (MMx) OA model results indicated the conditional knockout of Ezh2 deteriorated OA pathological conditions. Furthermore, we showed the positive role of Ezh2 in cartilage wound healing and inhibition of hypertrophy through activating TNFSF13B, a member of the tumor necrosis factor superfamily. Further, we also indicated that the effect of TNFSF13B, increased by Ezh2, might boost the healing of chondrocytes through increasing the phosphorylation of Akt. Taken together, our results uncovered an EZH2‐positive subpopulation existed in OA patients, and that EZH2‐TNFSF13B signaling was responsible for regulating chondrocyte healing and hypertrophy. Thus, EZH2 might act as a new potential target for OA diagnosis and treatment. © 2020 American Society for Bone and Mineral Research.