骨桥蛋白通过CD44和αvβ3整合素抑制自噬，并促进骨关节炎成纤维样滑膜细胞的增殖。

Osteopontin inhibits autophagy via CD44 and avβ3 integrin and promotes cell proliferation in osteoarthritic fibroblast-like synoviocytes.

作者信息

Li Min, Wei Chang-Bao, Li Hai-Feng, He Ke, Bai Rui-Jun, Zhang Fang-Jie

机构信息

Department of Orthopaedics, Wuxi Ninth People's Hospital, Soochow University, 999 Liangxi Road, Wuxi, Jiangsu, 214000, China.

Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China.

出版信息

BMC Musculoskelet Disord. 2025 Mar 18;26(1):274. doi: 10.1186/s12891-025-08509-y.

DOI:10.1186/s12891-025-08509-y

PMID:40102843

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11916941/

Abstract

OBJECTIVE

Osteoarthritis (OA) is closely related to aging, and autophagy is implicated in the retardation of aging. Activated synoviocytes play important roles in OA; the synoviocytes could produce osteopontin (OPN) and its main receptors CD44 and integrin, which are all involved in OA. The purpose of this study is to investigate whether OPN has an effect on autophagy in osteoarthritic synoviocytes.

METHODS

We cultured human OA fibroblast-like synoviocytes (FLS) and treated them with rhOPN and antibodies against CD44 and CD51/61 (αvβ3 integrin) or isotype IgG to block the interaction between receptors and ligands. Infection with lentivirus mRFP-GFP-LC3, laser confocal imaging and Western blotting were used to determine changes in the expression of autophagy markers, and cell proliferation of FLS was assessed with a CCK-8 assay.

RESULTS

Our results showed the expression level of autophagy marker protein LC3 II and the mRFP-GFP-LC3 puncta were significantly decreased after treatment with rhOPN when compared with the control group, when the FLS were incubated with antibodies against CD44 or CD51/61 (αvβ3 integrin) or with control isotype IgG for 1 h, followed by rhOPN treatment for 48 h, rhOPN could suppress the relative expression of LC3 II and Beclin1 via integrin and CD44 in the FLS, CCK-8 assay also showed that rhOPN significantly increased the cell proliferation and viability of FLS.

CONCLUSIONS

OPN could inhibit autophagy via CD44 and αvβ3 integrin and promote the proliferation of FLS, playing an important role in OA synovitis.

摘要

目的

骨关节炎（OA）与衰老密切相关，自噬参与延缓衰老过程。活化的滑膜细胞在OA中起重要作用；滑膜细胞可产生骨桥蛋白（OPN）及其主要受体CD44和整合素，这些均与OA有关。本研究旨在探讨OPN对骨关节炎滑膜细胞自噬是否有影响。

方法

我们培养人OA成纤维样滑膜细胞（FLS），并用重组人骨桥蛋白（rhOPN）、抗CD44和CD51/61（αvβ3整合素）抗体或同型IgG处理，以阻断受体与配体之间的相互作用。通过慢病毒mRFP-GFP-LC3感染、激光共聚焦成像和蛋白质印迹法来确定自噬标志物表达的变化，并用CCK-8法评估FLS的细胞增殖情况。

结果

我们的结果显示，与对照组相比，用rhOPN处理后自噬标志物蛋白LC3 II的表达水平和mRFP-GFP-LC3斑点明显降低。当FLS与抗CD44或CD51/61（αvβ3整合素）抗体或同型对照IgG孵育1小时，随后用rhOPN处理48小时，rhOPN可通过整合素和CD44抑制FLS中LC3 II和Beclin1的相对表达，CCK-8法也显示rhOPN显著增加了FLS的细胞增殖和活力。