Li Yugang, Xu Zechuan, Chang Shan
Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, No. 278 Baoguang Avenue, Xindu District, Chengdu 610500, Sichuan, People's Republic of China.
Department of Orthopedics, The Second Affiliated Hospital of Chengdu Medical College (Nuclear Industry 416 Hospital), Chengdu 610057, Sichuan, People's Republic of China.
Open Life Sci. 2021 Oct 26;16(1):1130-1140. doi: 10.1515/biol-2021-0102. eCollection 2021.
Osteonecrosis of the femoral head (ONFH) induced by glucocorticoids (GCs) has been considered to be associated with the dysfunction of bone marrow mesenchymal stem cells (BMSCs). Studies have reported that GCs can regulate the normal differentiation of BMSCs. However, the exact mechanism of this regulation remains unclear. In this study, we used methylprednisolone (MPS) to induce BMSCs, and then found that the Hippo signaling pathway was upregulated in a dose-dependent manner compared to that in the control group. In addition, the osteogenic ability of BMSCs was decreased, as evaluated by Alizarin Red S staining analysis and alkaline phosphatase activity assays, accompanied by the downregulated expression of Runx2, osteopontin, and osteocalcin. Additionally, the adipogenic capacity of BMSCs under the MPS conditions was increased, as identified by Oil Red O staining with upregulated triglyceride and PPARγ expression. Moreover, suppression by knockdown of MST1 was found to attenuate the Hippo signaling pathway and adipogenic differentiation, while enhancing osteogenic differentiation. In conclusion, our findings revealed that the Hippo signaling pathway was involved in GC-ONFH by affecting the osteogenic and adipogenic differentiation capacities of BMSCs. Our study could provide a basis for further investigation of the specific function of the Hippo pathway in ONFH.
糖皮质激素（GCs）诱导的股骨头坏死（ONFH）被认为与骨髓间充质干细胞（BMSCs）功能障碍有关。研究报道，GCs可调节BMSCs的正常分化。然而，这种调节的确切机制仍不清楚。在本研究中，我们使用甲基强的松龙（MPS）诱导BMSCs，然后发现与对照组相比，Hippo信号通路呈剂量依赖性上调。此外，通过茜素红S染色分析和碱性磷酸酶活性测定评估，BMSCs的成骨能力下降，同时Runx2、骨桥蛋白和骨钙素的表达下调。另外，通过油红O染色鉴定，在MPS条件下BMSCs的成脂能力增加，甘油三酯和PPARγ表达上调。此外，发现敲低MST1可抑制Hippo信号通路和成脂分化，同时增强成骨分化。总之，我们的研究结果表明，Hippo信号通路通过影响BMSCs的成骨和成脂分化能力参与GC-ONFH的发生。我们的研究可为进一步研究Hippo通路在ONFH中的具体作用提供依据。
