Department of Orthopedics, Shanghai Fifth People's Hospital, Fudan University, No128. Ruili Road, Minhang District, Shanghai, 200240, China.
Center of Community-Based Health Research, Fudan University, Shanghai, China.
Sci Rep. 2023 Apr 5;13(1):5589. doi: 10.1038/s41598-023-32868-y.
Femoral head necrosis is responsible for severe pain and its incidence is increasing. Abnormal adipogenic differentiation and fat cell hypertrophy of bone marrow mesenchymal stem cells increase intramedullary cavity pressure, leading to osteonecrosis. By analyzing gene expression before and after adipogenic differentiation, we found that Microfibril-Associated Protein 5 (MFAP5) is significantly down-regulated in adipogenesis whilst the mechanism of MFAP5 in regulating the differentiation of bone marrow mesenchymal stem cells is unknown. The purpose of this study was to clarify the role of MAFP5 in adipogenesis and therefore provide a theoretical basis for future therapeutic options of osteonecrosis. By knockdown or overexpression of MFAP5 in C3H10 and 3T3-L1 cells, we found that MFAP5 was significantly down-regulated as a key regulator of adipogenic differentiation, and identified the underlying downstream molecular mechanism. MFAP5 directly bound to and inhibited the expression of Staphylococcal Nuclease And Tudor Domain Containing 1, an essential coactivator of PPARγ, exerting an important regulatory role in adipogenesis.
股骨头坏死可引起严重疼痛,其发病率正在上升。骨髓间充质干细胞的异常脂肪生成分化和脂肪细胞肥大增加了髓腔内压力,导致骨坏死。通过分析脂肪生成前后的基因表达,我们发现 Microfibril-Associated Protein 5 (MFAP5) 在脂肪生成过程中显著下调,而 MFAP5 调节骨髓间充质干细胞分化的机制尚不清楚。本研究旨在阐明 MFAP5 在脂肪生成中的作用,为骨坏死的未来治疗选择提供理论依据。通过在 C3H10 和 3T3-L1 细胞中敲低或过表达 MFAP5,我们发现 MFAP5 作为脂肪生成分化的关键调节因子显著下调,并确定了潜在的下游分子机制。MFAP5 直接结合并抑制 Staphylococcal Nuclease And Tudor Domain Containing 1 的表达,后者是 PPARγ 的必需共激活因子,在脂肪生成中发挥重要的调节作用。