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

Overview

abstract

  • 1α,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] 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)(2)D(3) induced osteoclast formation in a dose-dependent manner, with maximum osteoclast formation observed at concentrations greater than 10(-9) M of 1,25(OH)(2)D(3). In the presence of bone morphogenetic protein 2 (BMP-2), the maximum formation of osteoclasts was seen with lower concentrations of 1,25(OH)(2)D(3) (greater than 10(-11) M), suggesting that BMP-2 enhances osteoclast formation induced by 1,25(OH)(2)D(3). In addition, the expressions of RANKL mRNA and proteins were induced by 1,25(OH)(2)D(3) in osteoblasts, and further upregulated by BMP-2. In mouse bone marrow cell cultures without 1,25(OH)(2)D(3), 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)(2)D(3).

publication date

  • October 13, 2010

Research

keywords

  • Bone Morphogenetic Protein 2
  • Osteoblasts
  • Osteoclasts
  • RANK Ligand

Identity

Scopus Document Identifier

  • 78649329687

Digital Object Identifier (DOI)

  • 10.1007/s00441-010-1052-y

PubMed ID

  • 20941510

Additional Document Info

volume

  • 342

issue

  • 2