RRC ID 44510
Author Horibe K, Nakamichi Y, Uehara S, Nakamura M, Koide M, Kobayashi Y, Takahashi N, Udagawa N.
Title Roles of cathelicidin-related antimicrobial peptide in murine osteoclastogenesis.
Journal Immunology
Abstract Cathelicidin-related antimicrobial peptide (CRAMP) not only kills bacteria but also binds to lipopolysaccharide (LPS) to neutralize its activity. CRAMP is highly expressed in bone marrow and its expression is reported to be up-regulated by inflammatory and infectious stimuli. Here, we examined the role of CRAMP in murine osteoclastogenesis. Osteoclasts were formed in co-cultures of osteoblasts and bone marrow cells in response to 1α,25-dihydroxyvitamin D3 [1α,25(OH)2 D3 ], prostaglandin E2 (PGE2 ), and Toll-like receptor (TLR) ligands such as LPS and flagellin through the induction of receptor activator of nuclear factor-κB ligand (RANKL) expression in osteoblasts. CRAMP inhibited the osteoclastogenesis in co-cultures treated with LPS and flagellin, but not in those treated with 1α,25(OH)2 D3 or PGE2 . Although bone marrow macrophages (BMMs) highly expressed formyl peptide receptor 2 (a receptor of CRAMP), CRAMP showed no inhibitory effect on osteoclastogenesis in BMM cultures treated with RANKL. CRAMP suppressed both LPS- and flagellin-induced RANKL expression in osteoblasts and tumour necrosis factor-α (TNF-α) expression in BMMs, suggesting that CRAMP neutralizes the actions of LPS and flagellin. LPS and flagellin enhanced the expression of CRAMP mRNA in osteoblasts. Extracellularly added CRAMP suppressed LPS- and flagellin-induced CRAMP expression. These results suggest that the production of CRAMP promoted by LPS and flagellin is inhibited by CRAMP released by osteoblasts through a feedback regulation. Even though CRAMP itself has no effect on osteoclastogenesis in mice, we propose that CRAMP is an osteoblast-derived protector in bacterial infection-induced osteoclastic bone resorption.
Volume 140(3)
Pages 344-51
Published 2013-11
DOI 10.1111/imm.12146
PMID 23826736
PMC PMC3800439
MeSH 24,25-Dihydroxyvitamin D 3 / immunology Animals Antimicrobial Cationic Peptides / immunology Bone Marrow Cells / immunology Bone Marrow Cells / metabolism Bone Resorption / etiology Bone Resorption / immunology* Cathelicidins / pharmacology Cathelicidins / physiology* Cells, Cultured Coculture Techniques Dinoprostone / immunology Feedback, Physiological Flagellin / immunology Lipopolysaccharides / immunology Male Mice Mice, Inbred Strains Osteoblasts / drug effects Osteoblasts / immunology* Osteoclasts / drug effects Osteoclasts / immunology* Osteogenesis / drug effects Osteogenesis / immunology* RANK Ligand / genetics RANK Ligand / metabolism Toll-Like Receptors / agonists Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism
IF 4.147
Times Cited 16
Human and Animal Cells