Wang Helin, Shi Yuqian, He Feng, Ye Tao, Yu Shibin, Miao Hui, Liu Qian, Zhang Mian
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases, Department of Medical Rehabilitation, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
Bone Joint Res. 2022 Jul;11(7):453-464. doi: 10.1302/2046-3758.117.BJR-2022-0019.R1.
Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). Growth differentiation factor 11 (GDF11) is crucial in inhibiting the differentiation of bone marrow mesenchymal stem cells into adipocytes. However, whether GDF11 participates in the abnormal adipogenesis of chondrocytes in OA cartilage is still unclear.
Six-week-old female mice were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical staining (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. Primary condylar chondrocytes of rats were stimulated with fluid flow shear stress (FFSS) and collected for oil red staining, immunofluorescence staining, qRT-PCR, and immunoprecipitation analysis.
Abnormal adipogenesis, characterized by increased expression of CCAAT/enhancer-binding protein α (CEBPα), fatty acid binding protein 4 (FABP4), Perilipin1, Adiponectin (AdipoQ), and peroxisome proliferator-activated receptor γ (PPARγ), was enhanced in the degenerative cartilage of TMJ OA in UAC mice, accompanied by decreased expression of GDF11. After FFSS stimulation, there were fat droplets in the cytoplasm of cultured cells with increased expression of PPARγ, CEBPα, FABP4, Perilipin1, and AdipoQ and decreased expression of GDF11. Exogenous GDF11 inhibited increased lipid droplets and expression of AdipoQ, CEBPα, and FABP4 induced by FFSS stimulation. GDF11 did not affect the change in PPARγ expression under FFSS, but promoted its post-translational modification by small ubiquitin-related modifier (SUMOylation). Local injection of GDF11 alleviated TMJ OA-related cartilage degeneration and abnormal adipogenesis in UAC mice.
Abnormal adipogenesis of chondrocytes and decreased GDF11 expression were observed in degenerative cartilage of TMJ OA. GDF11 supplementation effectively inhibits the adipogenesis of chondrocytes and thus alleviates TMJ condylar cartilage degeneration. GDF11 may inhibit the abnormal adipogenesis of chondrocytes by affecting the SUMOylation of PPARγ. Cite this article: 2022;11(7):453-464.
脂质代谢异常参与骨关节炎（OA）的发展。生长分化因子11（GDF11）在抑制骨髓间充质干细胞向脂肪细胞分化中起关键作用。然而，GDF11是否参与OA软骨中软骨细胞的异常脂肪生成仍不清楚。
对6周龄雌性小鼠进行单侧前牙反咬合（UAC）以诱导颞下颌关节（TMJ）骨关节炎。进行组织化学染色、免疫组织化学染色（IHC）和定量实时聚合酶链反应（qRT-PCR）。用流体流动剪切应力（FFSS）刺激大鼠原代髁突软骨细胞，并收集细胞进行油红染色、免疫荧光染色、qRT-PCR和免疫沉淀分析。
UAC小鼠TMJ OA退变软骨中，以CCAAT/增强子结合蛋白α（CEBPα）、脂肪酸结合蛋白4（FABP4）、 perilipin1、脂联素（AdipoQ）和过氧化物酶体增殖物激活受体γ（PPARγ）表达增加为特征的异常脂肪生成增强，同时GDF11表达降低。FFSS刺激后，培养细胞的细胞质中出现脂滴，PPARγ、CEBPα、FABP4、perilipin1和AdipoQ表达增加，GDF11表达降低。外源性GDF11抑制了FFSS刺激诱导的脂滴增加以及AdipoQ、CEBPα和FABP4的表达。GDF11不影响FFSS作用下PPARγ表达的变化，但通过小泛素相关修饰物促进其翻译后修饰（SUMO化）。局部注射GDF11可减轻UAC小鼠TMJ OA相关的软骨退变和异常脂肪生成。
在TMJ OA的退变软骨中观察到软骨细胞异常脂肪生成和GDF11表达降低。补充GDF11可有效抑制软骨细胞的脂肪生成，从而减轻TMJ髁突软骨退变。GDF11可能通过影响PPARγ的SUMO化来抑制软骨细胞的异常脂肪生成。引用本文：2022；11（7）：453 - 464。
