title: Acidosis inhibits mineralization in human osteoblasts.
abstract: Osteoblasts and osteoclasts maintain bone volume. Acidosis affects the function of these cells including mineral metabolism. We examined the effect of acidosis on the expression of transcription factors and mineralization in human osteoblasts in vitro. Human osteoblasts (SaM-1 cells) derived from the ulnar periosteum were cultured with α-MEM containing 50 μg/ml ascorbic acid and 5 mM β-glycerophosphate (calcifying medium). Acidosis was induced by incubating the SaM-1 cells in 10 % CO₂ (pH approximately 7.0). Mineralization, which was augmented by the calcifying medium, was completely inhibited by acidosis. Acidosis depressed c-Jun mRNA and increased osteoprotegerin (OPG) production in a time-dependent manner. Depressing c-Jun mRNA expression using siRNA increased OPG production and inhibited mineralization. In addition, depressing OPG mRNA expression with siRNA enhanced mineralization in a dose-dependent manner. Acidosis or the OPG protein strongly inhibited mineralization in osteoblasts from neonatal mice. The present study was the first to demonstrate that acidosis inhibited mineralization, depressed c-Jun mRNA expression, and induced OPG production in human osteoblasts. These results suggest that OPG is involved in mineralization via c-Jun in human osteoblasts.
authors.affiliation: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, 464-8650, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Koji
authors.initials: K
authors.lastname: Hirukawa
authors.forename: Akifumi
authors.initials: A
authors.lastname: Togari
mesh_terms: D000138:Acidosis / Q000473:pathology*; D000818:Animals; D002113:Calcification, Physiologic; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D005994:Glycerophosphates / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009930:Organic Chemicals / Q000737:chemistry; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D010521:Periosteum / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D014457:Ulna / Q000473:pathology
chemical_list: D003470:Culture Media; D016207:Cytokines; D005994:Glycerophosphates; D009930:Organic Chemicals; D053244:Osteoprotegerin; D016755:Proto-Oncogene Proteins c-jun; D053245:RANK Ligand; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C420642:alpha minimal essential medium; C031463:beta-glycerophosphoric acid