title: Phytocomponent p-hydroxycinnamic acid inhibits osteoclast-like cell formation in mouse bone marrow cultures.
abstract: 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.
authors.affiliation: Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, Yada, Shizuoka 422-8526, Japan.
authors.forename: Ying Ling
authors.initials: YL
authors.lastname: Lai
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yamaguchi
mesh_terms: 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
chemical_list: D003373:Coumaric Acids; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D011422:Propionates; D053245:RANK Ligand; C025940:bone resorption factor; C495469:p-coumaric acid