肌球蛋白 VI 介导体细胞功能，对于胶原诱导性关节炎中的关节损伤是必需的。

Myo6 mediates osteoclast function and is essential for joint damage in collagen-induced arthritis.

机构信息

SMU-KI United Medical Inflammatory Center, School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou 510515, China.

Department of Pharmacy, Jingzhou Central Hospital, Jingzhou, Hubei 434020, China.

出版信息

Biochim Biophys Acta Mol Basis Dis. 2024 Jan;1870(1):166902. doi: 10.1016/j.bbadis.2023.166902. Epub 2023 Oct 9.

DOI:10.1016/j.bbadis.2023.166902

PMID:37816396

Abstract

OBJECTIVES

To explore the novel function of MYO6 on Osteoclast differentiation and its joint destruction capacity in Rheumatoid arthritis mice model.

METHODS

We examined joint erosion in a collagen-induced arthritis (CIA) mouse model using micro-CT, with the mice having a MYO6 knockout background. Inflammatory cytokines were analyzed using an enzyme-linked immunosorbent assay (ELISA). In vitro, we investigated the osteoclastogenesis ability of bone marrow-derived macrophages isolated from MYO6 mice and their littermate controls, examining both morphological and functional differences. Furthermore, we explored podosome formation and endosome maturation using immunofluorescence staining.

RESULTS

We found that MYO6 deficiency attenuated arthritis development and bone destruction in CIA mice as well as impaired osteoclast differentiation by inhibiting NFATc1 induction. Our findings indicate that MYO6 is essential for the organization of podosomes by modulating the FAK/AKT and integrin-β3/Src pathways. MYO6 also mediates endosome transportation by regulating the expression of Rab5 and GM130. This may impact the maintenance and functionality of the ruffled border, as well as the regulation of autophagy in osteoclasts.

CONCLUSION

Our results demonstrated a critical function of MYO6 in osteoclast differentiation and its potential relevance in experimental arthritis.

摘要

目的

探讨肌球蛋白 VI（MYO6）在破骨细胞分化中的新功能及其在类风湿关节炎小鼠模型中的联合破坏能力。

方法

我们使用微 CT 检查胶原诱导关节炎（CIA）小鼠模型中的关节侵蚀，该模型具有 MYO6 基因敲除背景。采用酶联免疫吸附试验（ELISA）分析炎性细胞因子。在体外，我们研究了源自 MYO6 基因敲除小鼠及其同窝对照小鼠的骨髓来源巨噬细胞的破骨细胞生成能力，观察形态和功能差异。此外，我们还通过免疫荧光染色研究了足突形成和内体成熟。

结果

我们发现 MYO6 缺乏可抑制 NFATc1 诱导，从而减轻 CIA 小鼠的关节炎发展和骨破坏，并损害破骨细胞分化。我们的研究结果表明，MYO6 通过调节 FAK/AKT 和整合素-β3/Src 通路对足突的形成至关重要。MYO6 还通过调节 Rab5 和 GM130 的表达来介导内体运输。这可能影响破骨细胞的皱褶缘维持和功能以及自噬的调节。