title: Beta-glycerophosphate accelerates RANKL-induced osteoclast formation in the presence of ascorbic acid.
abstract: Despite numerous reports of the synergistic effects of beta-glycerophosphate and ascorbic acid in inducing the differentiation of osteoblasts, little is known about their roles in osteoclastic differentiation. Therefore, we investigated the effect of beta-glycerophosphate on osteoclastogenesis in the presence of ascorbic acid using primary mouse bone marrow cultures treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-kappaB ligand (RANKL). Beta-Glycerophosphate dose-dependently increased RANKL-induced osteoclast formation in the presence of ascorbic acid. This stimulatory effect was apparent when beta-glycerophosphate and ascorbic acid were only added during the late stages of the culture period, indicating that they influence later events in osteoclastic differentiation. While the combination of beta-glycerophosphate and ascorbic acid inhibited RANKL-stimulated activation of ERK and p38, and degradation of IkappaB, it increased the induction of c-Fos and NFATc1. In addition, beta-glycerophosphate and ascorbic acid together enhanced the induction of COX-2 following RANKL stimulation. Taken together, our data suggest that beta-glycerophosphate and ascorbic acid have synergistic effects on osteoclast formation, increasing RANKL-mediated induction of c-Fos, NFATc1 and COX-2 in osteoclast precursors.
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: A Long Sae Mi
authors.initials: AL
authors.lastname: Noh
authors.forename: Mijung
authors.initials: M
authors.lastname: Yim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005994:Glycerophosphates / Q000494:pharmacology*; D007202:Indicators and Reagents; D051379:Mice; D008813:Mice, Inbred ICR; D050778:NFATC Transcription Factors / Q000235:genetics; D010010:Osteoclasts / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005994:Glycerophosphates; D007202:Indicators and Reagents; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D051546:Cyclooxygenase 2; D001205:Ascorbic Acid