Medical School, University of Chinese Academy of Sciences, Beijing, China.
Cell Biochem Funct. 2020 Jan;38(1):87-96. doi: 10.1002/cbf.3457. Epub 2019 Oct 31.
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.
未羧化骨钙素（unOc）是一种成骨细胞衍生的激素，具有多种调节功能。骨钙素敲低会延迟矿物质物种的成熟，并下调人间充质基质细胞中成骨特异性基因的表达。然而，其潜在机制尚不清楚。在这里，我们研究了 unOc 对小鼠骨髓间充质干细胞（BMSCs）成骨分化的影响，发现 unOc 促进了 BMSCs 的成骨分化，其特征是碱性磷酸酶（ALP）活性、I 型胶原（COLI）产生、钙化结节形成以及成骨特异性基因的表达增加，包括成骨特异性转录因子 2（Runx2）、ALP 和 COLI 基因。进一步的实验表明，unOc 通过激活 Erk-Smad/β-catenin 信号通路促进 BMSCs 的成骨分化。研究的意义：骨质疏松症与 BMSCs 的成骨分化有关。近年来，unOc 作为一种内分泌激素的功能受到了广泛关注。在这项研究中，我们首次报道了 unOc 通过 Erk-Smad/β-catenin 信号通路促进小鼠 BMSCs 的成骨分化。我们的结果强调了 unOc 作为一种促进 BMSCs 成骨分化的激素的重要性，表明该激素可能有益于骨质疏松症和骨折愈合的治疗。
