RRC ID 79436
Author Kanatani M, Sugimoto T, Kaji H, Kobayashi T, Nishiyama K, Fukase M, Kumegawa M, Chihara K.
Title Stimulatory effect of bone morphogenetic protein-2 on osteoclast-like cell formation and bone-resorbing activity.
Journal J Bone Miner Res
Abstract Although the action of bone morphogenetic protein (BMP) on osteoblast differentiation has been extensively investigated, its effect on osteoclast differentiation remains unknown. In the present study, in vitro effects of BMP-2 on osteoclast-like cell formation and bone resorption were examined. BMP-2 (1-100 ng/ml) significantly stimulated bone resorption by preexistent osteoclast-like cells in mouse bone cell cultures containing stromal cells, whereas it did not affect the bone-resorbing activity of isolated rabbit osteoclast-like cells. When BMP-2 was added to unfractionated bone cells after degeneration of preexistent osteoclast-like cells, BMP-2 dose-dependently stimulated osteoclast-like formation at a minimal effective concentration of 10 pg/ml. BMP-2 also enhanced the osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Moreover, osteoclast-like cells newly formed by BMP-2 from unfractionated bone cells possessed the ability to form pits on dentine slices. Because these results indicated that BMP-2 directly or indirectly stimulated osteoclast differentiation and activity, we next examined the direct effect of BMP-2 on osteoclast precursors in the absence of stromal cells using hemopoietic blast cells derived from spleen cells. The mRNA for BMP-2/4 receptor was detected in hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as osteoblastic MC3T3-E1 cells and MC3T3-G2/PA6 stromal cells by RNase protection assay. BMP-2 dose-dependently stimulated osteoclast-like cell formation from hemopoietic blast cells supported by GM-CSF at a minimal effective concentration of 10 pg/ml. BMP-2 also enhanced 1,25(OH)2D3-induced osteoclast-like formation from hemopoietic blast cells. The present data are the first to indicate that BMP-2 stimulates bone resorption through both direct stimulation of osteoclast formation and activation of mature osteoclasts, possibly via stomal cells, in vitro.
Volume 10(11)
Pages 1681-90
Published 1995-11-1
DOI 10.1002/jbmr.5650101110
PMID 8592944
MeSH 3T3 Cells Animals Bone Morphogenetic Protein Receptors Bone Morphogenetic Proteins Bone Resorption / chemically induced* Calcitriol / pharmacology Cell Differentiation / drug effects Cells, Cultured Dose-Response Relationship, Drug Granulocyte-Macrophage Colony-Stimulating Factor / metabolism Growth Substances / pharmacology* Mice Osteoclasts / cytology Osteoclasts / drug effects* Proteins / pharmacology* RNA, Messenger / metabolism Rabbits Receptors, Cell Surface / metabolism Receptors, Growth Factor* Spleen / cytology
IF 5.854
Human and Animal Cells 10T1/2(RCB0247)