Abstract
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) indirectly stimulates bone formation, but little is known about its direct effect on bone formation. In this study, we observed that 1,25(OH)2D3 enhances adipocyte differentiation, but inhibits osteoblast differentiation during osteogenesis. The positive role of 1,25(OH)2D3 in adipocyte differentiation was confirmed when murine osteoblasts were cultured in adipogenic medium. Additionally, 1,25(OH)2D3 enhanced the expression of adipocyte marker genes, but inhibited the expression of osteoblast marker genes in osteoblasts. The inhibition of osteoblast differentiation and promotion of adipocyte differentiation mediated by 1,25(OH)2D3 were compensated by Runx2 overexpression. Our results suggest that 1,25(OH)2D3 induces the transdifferentiation of osteoblasts to adipocytes via Runx2 downregulation in osteoblasts.
Highlights
Bone is an important organ for supporting the body and regulating mineral homeostasis
To elucidate the direct effect of locally produced 1,25(OH)2D3 on bone formation, we investigated the effect of 1,25(OH)2D3 on osteoblast differentiation, Runx2 expression, and the transdifferentiation of osteoblasts to adipocytes
To elucidate the direct effect of 1,25(OH)2D3 on bone formation, we examined its role in osteoblast differentiation
Summary
Bone is an important organ for supporting the body and regulating mineral homeostasis. Osteoclasts resorb old bone and osteoblasts produce the bone matrix [2,3] Various factors, such as the paratyroid hormone and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), regulate bone homeostasis by modulating bone cells [2,4]. 1,25(OH)2D3 increases calcium absorption from the intestines, which indirectly stimulates bone formation [6] It can directly influence bone formation via the regulation of osteoblast differentiation and function. Osteoblasts, which are responsible for bone formation, are derived from mesenchymal stem cells by the action of several transcription factors, including Runx, osterix, and β-catenin [12]. Runx promotes the acquisition of an osteoblastic phenotype by mesenchymal stem cells by inducing the expression of genes encoding major bone matrix proteins, e.g., Col1a1, osteopontin, bone sialoprotein (BSP), and osteocalcin [11,12]. To elucidate the direct effect of locally produced 1,25(OH)2D3 on bone formation, we investigated the effect of 1,25(OH)2D3 on osteoblast differentiation, Runx expression, and the transdifferentiation of osteoblasts to adipocytes
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