Dexamethasone inhibits the formation of multinucleated osteoclasts via down-regulation of beta3 integrin expression.
Although glucocorticoids are known to affect osteoclast differentiation and function, there have been conflicting reports about the effect of glucocorticoids on osteoclast formation, leading to the assumption that microenvironment and cell type influence their action. We explored the effect of the synthetic glucocorticoid analog dexamethasone on the formation of osteoclasts. Dexamethasone inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts without affecting the formation of TRAP-positive mononuclear cells in a coculture of mouse osteoblasts and bone marrow cells. Dexamethasone did not inhibit mRNA expression levels of the receptor activator of nuclear factor-kappaB ligand and osteoprotegerin, the essential regulators of osteoclastogenesis. Dexamethasone down-regulated the expression of beta3 integrin mRNA and protein but did not alter expression of other osteoclast differentiation marker genes. Both dexamethasone and echistatin, a beta3 integrin function blocker, inhibited TRAP-positive multinucleated osteoclast formation but not TRAP-positive mononuclear cell formation. These results suggest that dexamethasone inhibits the formation of multinucleated osteoclasts, at least in part, through the down-regulation of beta3 integrin, which plays an important role in the formation of multinucleated osteoclasts.
Kim
Yong Hee
YH
Department of Cell and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
Jun
Ji-Hae
JH
Woo
Kyung Mi
KM
Ryoo
Hyun-Mo
HM
Kim
Gwan-Shik
GS
Baek
Jeong-Hwa
JH
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D005938:Glucocorticoids / Q000494:pharmacology*; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D053244:Osteoprotegerin / Q000096:biosynthesis; D053245:RANK Ligand / Q000096:biosynthesis
D015415:Biomarkers; D005938:Glucocorticoids; D039302:Integrin alphaVbeta3; D053244:Osteoprotegerin; D053245:RANK Ligand; C506031:Tnfrsf11b protein, mouse; D003907:Dexamethasone