G-protein-coupled receptor 124 promotes osteogenic differentiation of BMSCs through the Wnt/β-catenin pathway

In Vitro Cell Dev Biol Anim. 2022 Aug;58(7):529-538. doi: 10.1007/s11626-022-00684-9. Epub 2022 Aug 2.

Abstract

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.

Keywords: BMSC; GPR124; Osteogenic differentiation; Osteoporosis; Wnt/β-catenin.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Female
  • Humans
  • Mesenchymal Stem Cells*
  • Osteogenesis / genetics
  • Osteoporosis* / genetics
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Wnt Signaling Pathway / genetics
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Biomarkers
  • Receptors, G-Protein-Coupled
  • beta Catenin