Bone Morphogenetic Protein-7 (OP1) and Transforming Growth Factor-β1 Modulate 1,25(OH)₂-Vitamin D₃-Induced Differentiation of Human Osteoblasts

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• 作者：Eichner ; Annegret ; Brock ; Josef ; Heldin ; Carl-Henrik ; Souchelnytskyi ; Serhiy
• 刊名：Experimental Cell Research
• 出版年：2002
• 出版时间：April 15, 2002
• 年：2002
• 卷：275
• 期：1
• 页码：132-142
• 全文大小：768 K

文摘

Bone morphogenetic proteins (BMPs) and transforming growth factor-β (TGFβ) are potent regulators of osteoblast differentiation and proliferation, processes that are crucial in bone remodeling. BMPs and TGFβ act in concert with other local factors and hormones, among them 1,25(OH)₂-vitamin D₃ and insulin. Here we show that BMP7 inhibits 1,25(OH)₂-vitamin D₃-induced differentiation of human osteoblasts, whereas TGFβ1 stimulates it, as assessed by assays for alkaline phosphatase (ALP) induction, matrix mineralization, and morphology changes. BMP7 or TGFβ1 alone affects the differentiation of human osteoblasts. Similar results were obtained in assays for ALP induction using conditionally immortalized human osteoblasts (hFOB) and primary osteoblasts obtained from trabecular bone of the femoral head after hip replacement surgery. BMP7 stimulation led to a decrease of 1,25(OH)₂-vitamin D₃-induced binding of nuclear proteins to a vitamin D response element, as shown by electrophoretic mobility shift assay. Our results suggest that 1,25(OH)₂-vitamin D₃ modulates in opposite ways the effects of BMP7 and TGFβ1 on osteoblast differentiation.