Quercetin suppresses bone resorption by inhibiting the differentiation and activation of osteoclasts.
Although quercetin has suppressed bone resorption in several animal studies, its target cells and the mechanism of its action related to bone resorption has not been fully elucidated. We investigated the effect of quercetin on the differentiation and activation of osteoclasts. We used cocultures of mouse spleen cells and ST2 cells, and cultures of osteoclast progenitor cells [M-CSF-dependent (MD) cells from mouse bone marrow and murine monocytic RAW 264 (RAW) cells]. Quercetin dose-dependently inhibited osteoclast-like (OCL) cell formation at 2-5 microM concentration in both the coculture and MD cell culture. Quercetin inhibited the increase of tartrate-resistant acid phosphatase (TRAP) activity of mononuclear preosteoclasts (pOCs) induced by receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL) in both MD and RAW cell cultures. Quercetin reversely induced the disruption of actin rings in OCLs. Quercetin also suppressed both pit formation induced by osteoclasts on dentine slices and PTH-stimulated (45)Ca release in mouse long bone cultures. These results suggest that osteoclast progenitors as well as mature osteoclasts, are quercetin's target cells in relation to bone resorption, and that quercetin's suppressive effect on bone resorption results from both its inhibitory effect on the differentiation of osteoclast progenitor cells into pOCs and from its disruptive effect on actin rings in mature osteoclasts.
Woo
Je-Tae
JT
Department of Biological Chemistry, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan. jwoo@isc.chubu.ac.jp
Nakagawa
Hiroshi
H
Notoya
Michitaka
M
Yonezawa
Takayuki
T
Udagawa
Nobuyuki
N
Lee
In-Seon
IS
Ohnishi
Motoko
M
Hagiwara
Hiromi
H
Nagai
Kazuo
K
D000135:Acid Phosphatase / Q000378:metabolism; D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D001862:Bone Resorption / Q000473:pathology / Q000517:prevention & control*; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000071681:Tartrate-Resistant Acid Phosphatase
D000199:Actins; D002352:Carrier Proteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D011794:Quercetin; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase