Department of Orthopedics, The First Hospital of Yulin, Yulin, 719000, People's Republic of China.
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
In Vitro Cell Dev Biol Anim. 2022 Aug;58(7):529-538. doi: 10.1007/s11626-022-00684-9. Epub 2022 Aug 2.
Osteoporosis occurs frequently in women after menopause and old age, and it is very easy to cause osteoporotic fractures, resulting in disability and death. In osteoporosis patients, the potential of bone marrow mesenchymal stem cells (BMSCs) to differentiate into osteoblasts gradually is inhibited, leading to decreased new bone formation. In the current study, the potential effect of G-protein-coupled receptor 124 (GPR124) on the osteoblastic differentiation of BMSCs was determined. BMSCs were isolated and cultured in osteogenic media to induced osteogenic differentiation. Then, osteogenic differentiation was evaluated by Alizarin Red staining and ALP activity. The expression of osteogenic differentiation biomarkers, and Wnt/β-catenin signaling were determined by qRT-PCR and Western blotting. The results indicated that the expression of GPR124 was significantly increased during osteogenic differentiation of BMSCs. Moreover, GPR124 knockdown significantly inhibited osteoblastic differentiation and GPR124 overexpression promoted osteoblastic differentiation of BMSCs. GPR124 knockdown suppressed the activation of Wnt/β-catenin signaling pathway. What's more, the increased osteogenic differentiation induced by GPR124 overexpression was abolished by the inhibitor of Wnt/β-catenin pathway and Wnt7a knockdown. Taken together, GPR124 promotes osteogenic differentiation of BMSCs through the Wnt/β-catenin pathway and may serve as a potential target for enhancing osteogenesis of osteoporosis patients.
骨质疏松症在绝经后和老年妇女中很常见,很容易导致骨质疏松性骨折,导致残疾和死亡。在骨质疏松症患者中,骨髓间充质干细胞(BMSCs)向成骨细胞分化的潜能逐渐受到抑制,导致新骨形成减少。在本研究中,确定了 G 蛋白偶联受体 124(GPR124)对 BMSCs 成骨分化的潜在影响。分离并培养 BMSCs 在成骨培养基中诱导成骨分化。然后,通过茜素红染色和 ALP 活性评估成骨分化。通过 qRT-PCR 和 Western blot 测定成骨分化生物标志物和 Wnt/β-catenin 信号的表达。结果表明,GPR124 的表达在 BMSCs 的成骨分化过程中显著增加。此外,GPR124 敲低显著抑制成骨分化,而 GPR124 过表达促进 BMSCs 的成骨分化。GPR124 敲低抑制了 Wnt/β-catenin 信号通路的激活。更重要的是,GPR124 过表达诱导的成骨分化增加被 Wnt/β-catenin 通路抑制剂和 Wnt7a 敲低所消除。综上所述,GPR124 通过 Wnt/β-catenin 通路促进 BMSCs 的成骨分化,可能成为增强骨质疏松症患者成骨的潜在靶点。