RRC ID 62096
Author Murakami T, Yamamoto M, Ono K, Nishikawa M, Nagata N, Motoyoshi K, Akatsu T.
Title Transforming growth factor-beta1 increases mRNA levels of osteoclastogenesis inhibitory factor in osteoblastic/stromal cells and inhibits the survival of murine osteoclast-like cells.
Journal Biochem Biophys Res Commun
Abstract Osteoclastogenesis inhibitory factor (OCIF), also termed osteoprotegerin (OPG), is a secreted member of the tumor necrosis factor (TNF) receptor family. It inhibits bone resorption in vivo and osteoclast-like cell (OCL) formation in vitro. To better understand the biological role of OCIF, we first examined the effects of various osteotropic agents on OCIF mRNA levels in mouse calvarial osteoblasts. Northern blot analysis showed that stimulators of OCL formation such as 1,25-(OH)2D3, prostaglandin E2 (PGE2), parathyroid hormone (PTH), and interleukin 1 (IL-1) decreased OCIF mRNA levels. In contrast, transforming growth factor (TGF)-beta1 increased OCIF mRNA levels in primary osteoblasts as well as in osteoblastic/stromal cell lines. Since it was reported that both TGF-beta1 and OCIF not only inhibited OCL formation but also impaired the survival of OCL by inducing apoptosis in vitro, we next examined the possible involvement of OCIF in TGF-beta1-induced impairment of OCL survival. In a mouse bone marrow culture, we confirmed that addition of OCIF or TGF-beta1 decreased the number of surviving OCL. Anti-OCIF IgG, which completely neutralized the effect of OCIF, partially prevented the TGF-beta1-induced decrease in the number of OCL. Our results suggest that (i) downregulation of OCIF expression is one of the mechanisms for the stimulatory effects of 1,25(OH)2D3, PGE2, PTH, and IL-1 on osteoclastogenesis; and (ii) the TGF-beta1-induced apoptosis of OCL is mediated, at least in part, by upregulation of OCIF expression.
Volume 252(3)
Pages 747-52
Published 1998-11-27
DOI 10.1006/bbrc.1998.9723
PII S0006-291X(98)99723-6
PMID 9837778
MeSH Animals Cell Survival / drug effects Cells, Cultured Dexamethasone / pharmacology Glucocorticoids / pharmacology Glycoproteins / biosynthesis* Glycoproteins / genetics Humans Immune Sera Immunoglobulin G / metabolism Mice Osteoblasts / drug effects* Osteoblasts / metabolism Osteoclasts / cytology* Osteoclasts / drug effects Osteoprotegerin RNA, Messenger / metabolism* Rabbits Receptors, Cytoplasmic and Nuclear* Receptors, Tumor Necrosis Factor / biosynthesis* Receptors, Tumor Necrosis Factor / genetics Recombinant Proteins / metabolism Stromal Cells / drug effects Stromal Cells / metabolism Transforming Growth Factor beta / pharmacology*
IF 2.985
Human and Animal Cells MC3T3-E1(RCB1126) ST2(RCB0224)