Phytocomponent p-hydroxycinnamic acid inhibits osteoclast-like cell formation in mouse bone marrow cultures

Int J Mol Med. 2007 Jan;19(1):123-8.

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.

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / physiology
  • Cell Differentiation
  • Coumaric Acids / pharmacology*
  • Cytokines / pharmacology
  • Drug Interactions
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Mice
  • Osteoclasts / drug effects*
  • Osteoclasts / physiology
  • Propionates
  • RANK Ligand / physiology

Substances

  • Coumaric Acids
  • Cytokines
  • Intracellular Signaling Peptides and Proteins
  • Propionates
  • RANK Ligand
  • bone resorption factor
  • p-coumaric acid