Phytocomponent p-hydroxycinnamic acid inhibits osteoclast-like cell formation in mouse bone marrow cultures.
The phytocomponent p-hydroxycinnamic acid (HCA) has been shown to have inhibitory effects on bone-resorbing factor-stimulated bone resorption in rat femoral tissues in vitro. The effects of HCA on osteoclast-like cell formation in mouse bone marrow cultures in vitro were investigated. The bone marrow cells were cultured for 7 days in alpha-minimal essential medium containing a bone-resorbing agent [parathyroid hormone (1-34)] (PTH), prostaglandin E2 (PGE2), or tumor necrosis factor-alpha (TNF-alpha) in effective concentrations. Osteoclast-like cell formation was estimated by staining for tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts. The presence of PTH (10(-7) M), PGE2 (10(-5) M), or TNF-alpha (10 ng/ml) induced a remarkable increase in osteoclast-like multinucleated cells. These increases were significantly inhibited in the presence of HCA (10(-8)-10(-5) M). HCA (10(-6) or 10(-5) M) significantly inhibited osteoclast-like cell formation induced by dibutyryl cyclic adenosine monophosphate (10(-5) M) or phorbol 12-myristate 13-acetate (10(-6) M), an activator of protein kinase C. Also, HCA (10(-8)-10(-5) M) had a significant inhibitory effect on osteoclast-like cell formation induced by the receptor activator of NF-kappaB ligand (RANKL) (10 ng/ml) in the presence of macrophage colony-stimulating factor (M-CSF) (10 ng/ml). The inhibitory effect of HCA (10(-6) or 10(-5) M) on RANKL plus M-CSF-induced osteoclast-like cell formation was not observed in the presence of cycloheximide (10(-7) M), an inhibitor of protein synthesis in the transcriptional process, or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (10(-6) M), an inhibitor of transcription. This study demonstrates that HCA has a potent inhibitory effect on osteoclast-like cell formation in mouse bone marrow cultures. The inhibitory action of HCA may partly involve a newly synthesized protein component which is related to RANKL stimulation in osteoclastogenesis.
Lai
Ying Ling
YL
Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, Yada, Shizuoka 422-8526, Japan.
Yamaguchi
Masayoshi
M
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation; D003373:Coumaric Acids / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D004347:Drug Interactions; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D011422:Propionates; D053245:RANK Ligand / Q000502:physiology
D003373:Coumaric Acids; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D011422:Propionates; D053245:RANK Ligand; C025940:bone resorption factor; C495469:p-coumaric acid