Uncarboxylated osteocalcin promotes osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells by activating the Erk-Smad/β-catenin signalling pathways.

Uncarboxylated osteocalcin (unOc) is an osteoblast-derived hormone with multiple regulatory functions. Osteocalcin knockdown delays the maturation of mineral species and downregulates the expression of osteogenic-specific genes in human mesenchymal stromal cells. However, the underlying mechanisms remain unclear. Here, we investigated the effects of unOc on the osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (BMSCs) and discovered that unOc promoted osteogenic differentiation of BMSCs, which was characterized by increases in alkaline phosphatase (ALP) activity, type I collagen (COLI) production, calcified nodule formation, and expression of osteogenic-specific genes including the osterix, runt-related transcription factor 2 (Runx2), ALP, and COLI genes. Further experiments indicated that unOc promoted the osteogenic differentiation of BMSCs via activation of the Erk-Smad/β-catenin signalling pathways. SIGNIFICANCE OF THE STUDY: Osteoporosis is associated with the osteogenic differentiation of BMSCs. In recent years, the role of unOc function as an endocrine hormone has received much attention. In this study, we reported for the first time that unOc promoted the osteogenic differentiation of mouse BMSCs through Erk-Smad/β-catenin signalling pathway. Our results highlight the importance of unOc as a hormone in promoting the osteogenic differentiation of BMSCs, indicating that this hormone may be beneficial in treatments for osteoporosis and fracture healing.