Bone morphogenetic protein 2 enhances mouse osteoclast differentiation via increased levels of receptor activator of NF-κB ligand expression in osteoblasts

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作者：

K Tachi，M Takami，B Zhao，A Mochizuki，A Yamada，Y Miyamoto，T Inoue，K Baba，R Kamijo

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摘要：

1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] induces osteoclast formation via induction of receptor activator of NF-κB ligand (RANKL, also called TNF-related activation-induced cytokine: TRANCE) in osteoblasts. In cocultures of mouse bone marrow cells and osteoblasts, 1,25(OH)2D3 induced osteoclast formation in a dose-dependent manner, with maximum osteoclast formation observed at concentrations greater than 109M of 1,25(OH)2D3. In the presence of bone morphogenetic protein 2 (BMP-2), the maximum formation of osteoclasts was seen with lower concentrations of 1,25(OH)2D3 (greater than 1011M), suggesting that BMP-2 enhances osteoclast formation induced by 1,25(OH)2D3. In addition, the expressions of RANKL mRNA and proteins were induced by 1,25(OH)2D3 in osteoblasts, and further upregulated by BMP-2. In mouse bone marrow cell cultures without 1,25(OH)2D3, BMP-2 did not enhance osteoclast differentiation induced by recombinant RANKL and macrophage colony-stimulating factor (M-CSF), indicating that BMP-2 does not target osteoclast precursors. Furthermore, BMP-2 up-regulated the expression level of vitamin D receptor (VDR) in osteoblasts. These results suggest that BMP-2 regulates mouse osteoclast differentiation via upregulation of RANKL in osteoblasts induced by 1,25(OH)2D3.

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关键词：

Osteoclasts Osteoblasts Bone morphogenetic protein (BMP)-2 Receptor activator of NF-κB ligand (RANKL 1α,25-dihydroxyvitamin D3 Mouse (ddy

DOI：

10.1007/s00441-010-1052-y

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年份：

2010