Treatment of myoblastic C2C12 cells with BMP-2 stimulates vitamin D-induced formation of osteoclasts

• Published in: Calcified tissue international 2003-07, Vol.73 (1), p.72-77
• Main Authors: Otsuka, E, Notoya, M, Hagiwara, H
• Format: Article
• Language: English
• Subjects: Acid Phosphatase - metabolism; Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins - pharmacology; Carrier Proteins - biosynthesis; Carrier Proteins - genetics; Cell Differentiation - drug effects; Cell Line; Dose-Response Relationship, Drug; Drug Combinations; Giant Cells - drug effects; Giant Cells - enzymology; Isoenzymes - metabolism; Male; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Mice; Mice, Inbred Strains; Myoblasts - drug effects; Myoblasts - enzymology; Osteoclasts - drug effects; Osteoclasts - enzymology; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; RNA, Messenger - metabolism; Tartrate-Resistant Acid Phosphatase; Transforming Growth Factor beta - pharmacology; Vitamin D - analogs & derivatives; Vitamin D - pharmacology
• ISSN: 0171-967X; 1432-0827
• DOI: 10.1007/s00223-002-1071-0

The interaction of osteoclast precursors with osteoblasts and/or stromal cells is essential for the formation of mature osteoclasts and the resorption of bone. We found that myoblastic C2C12 cells induced the differentiation of mouse spleen cells into tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated cells in the presence of 10(-7) M 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and that C2C12 cells that had been treated with bone morphogenetic protein-2 (BMP-2) dose-dependently stimulated the formation of osteoclasts. The newly developed TRAP-positive multinucleated cells were capable of resorbing mineralized tissues. Treatment of C2C12 cells with BMP-2 for 24 h enhanced the subsequent expression in C2C12 cells of mRNA for the receptor activator of nuclear factor-kappaB ligand (RANKL) in the presence of 1alpha,25(OH)2D3. Since the formation of osteoclasts was inhibited dose-dependently by exogenous OPG, the expression of RANKL in response to BMP-2 appeared to be critical for the formation of osteoclasts. Our findings suggest that BMP-2 might play an important role in the differentiation of cells that support osteoclastogenesis.