RRC ID 38930
Author Romas E, Udagawa N, Zhou H, Tamura T, Saito M, Taga T, Hilton DJ, Suda T, Ng KW, Martin TJ.
Title The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures.
Journal J Exp Med
Abstract Interleukin (IL)-11 is a multifunctional cytokine whose role in osteoclast development has not been fully elucidated. We examined IL-11 production by primary osteoblasts and the effects of rat monoclonal anti-mouse glycoprotein 130 (gp130) antibody on osteoclast formation, using a coculture of mouse osteoblasts and bone marrow cells. IL-1, TNF alpha, PGE2, parathyroid hormone (PTH) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) similarly induced production of IL-11 by osteoblasts, but IL-6, IL-4, and TGF beta did not. Primary osteoblasts constitutively expressed mRNAs for both IL-11 receptor (IL-11R alpha) and gp130. Osteotropic factors did not modulate IL-11R alpha mRNA at 24 h, but steady-state gp130 mRNA expression in osteoblasts was upregulated by 1 alpha,25(OH)2D3, PTH, or IL-1. In cocultures, the formation of multinucleated osteoclast-like cells (OCLs) in response to IL-11, or IL-6 together with its soluble IL-6 receptor was dose-dependently inhibited by rat monoclonal anti-mouse gp130 antibody. Furthermore, adding anti-gp130 antibody abolished OCL formation induced by IL-1, and partially inhibited OCL formation induced by PGE2, PTH, or 1 alpha,25(OH)2D3. During osteoclast formation in marrow cultures, a sequential relationship existed between the expression of calcitonin receptor mRNA and IL-11R alpha mRNA. Osteoblasts as well as OCLs expressed transcripts for IL-11R alpha, as indicated by RT-PCR analysis and in situ hybridization. These results suggest a central role of gp130-coupled cytokines, especially IL-11, in osteoclast development. Since osteoblasts and mature osteoclasts expressed IL-11R alpha mRNA, both bone-forming and bone-resorbing cells are potential targets of IL-11.
Volume 183(6)
Pages 2581-91
Published 1996-6-1
DOI 10.1084/jem.183.6.2581
PMID 8676079
PMC PMC2192607
MeSH Animals Animals, Newborn Antibodies, Monoclonal / pharmacology Antigens, CD / immunology Antigens, CD / physiology* Base Sequence Bone Marrow / immunology* Bone Marrow Cells Calcitriol / pharmacology Cells, Cultured Coculture Techniques Cytokine Receptor gp130 Cytokines / pharmacology* DNA Primers Dinoprostone / pharmacology Humans In Situ Hybridization Interleukin-1 / pharmacology Interleukin-11 / biosynthesis* Interleukin-11 Receptor alpha Subunit Kinetics Male Membrane Glycoproteins / immunology Membrane Glycoproteins / physiology* Mice Mice, Inbred C57BL Molecular Sequence Data Osteoblasts / cytology Osteoblasts / drug effects Osteoblasts / immunology* Parathyroid Hormone / pharmacology Polymerase Chain Reaction RNA, Messenger / biosynthesis Rats Receptors, Interleukin / metabolism* Receptors, Interleukin-11 Recombinant Proteins / pharmacology Signal Transduction Time Factors Transcription, Genetic Tumor Necrosis Factor-alpha / pharmacology
IF 11.743
Times Cited 145
Human and Animal Cells ST2(RCB0224)