PMID- 23826736 OWN - NLM STAT- MEDLINE DCOM- 20131211 LR - 20221207 IS - 1365-2567 (Electronic) IS - 0019-2805 (Print) IS - 0019-2805 (Linking) VI - 140 IP - 3 DP - 2013 Nov TI - Roles of cathelicidin-related antimicrobial peptide in murine osteoclastogenesis. PG - 344-51 LID - 10.1111/imm.12146 [doi] AB - 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 1alpha,25-dihydroxyvitamin D3 [1alpha,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-kappaB ligand (RANKL) expression in osteoblasts. CRAMP inhibited the osteoclastogenesis in co-cultures treated with LPS and flagellin, but not in those treated with 1alpha,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-alpha (TNF-alpha) 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. CI - (c) 2013 John Wiley & Sons Ltd. FAU - Horibe, Kanji AU - Horibe K AD - Graduate School of Oral Medicine, Matsumoto Dental University, Nagano, Japan. FAU - Nakamichi, Yuko AU - Nakamichi Y FAU - Uehara, Shunsuke AU - Uehara S FAU - Nakamura, Midori AU - Nakamura M FAU - Koide, Masanori AU - Koide M FAU - Kobayashi, Yasuhiro AU - Kobayashi Y FAU - Takahashi, Naoyuki AU - Takahashi N FAU - Udagawa, Nobuyuki AU - Udagawa N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Antimicrobial Cationic Peptides) RN - 0 (Cathelicidins) RN - 0 (Lipopolysaccharides) RN - 0 (RANK Ligand) RN - 0 (Toll-Like Receptors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 12777-81-0 (Flagellin) RN - 40013-87-4 (24,25-Dihydroxyvitamin D 3) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - 24,25-Dihydroxyvitamin D 3/immunology MH - Animals MH - Antimicrobial Cationic Peptides/immunology MH - Bone Marrow Cells/immunology/metabolism MH - Bone Resorption/etiology/*immunology MH - Cathelicidins/pharmacology/*physiology MH - Cells, Cultured MH - Coculture Techniques MH - Dinoprostone/immunology MH - Feedback, Physiological MH - Flagellin/immunology MH - Lipopolysaccharides/immunology MH - Male MH - Mice MH - Mice, Inbred Strains MH - Osteoblasts/drug effects/*immunology MH - Osteoclasts/drug effects/*immunology MH - Osteogenesis/drug effects/*immunology MH - RANK Ligand/genetics/metabolism MH - Toll-Like Receptors/agonists MH - Tumor Necrosis Factor-alpha/genetics/metabolism PMC - PMC3800439 OTO - NOTNLM OT - cathelicidin-related antimicrobial peptide OT - flagellin OT - lipopolysaccharide OT - osteoclastogenesis OT - receptor activator of nuclear factor-kappaB ligand EDAT- 2013/07/06 06:00 MHDA- 2013/12/16 06:00 PMCR- 2014/11/01 CRDT- 2013/07/06 06:00 PHST- 2013/02/25 00:00 [received] PHST- 2013/06/20 00:00 [revised] PHST- 2013/07/01 00:00 [accepted] PHST- 2013/07/06 06:00 [entrez] PHST- 2013/07/06 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] PHST- 2014/11/01 00:00 [pmc-release] AID - 10.1111/imm.12146 [doi] PST - ppublish SO - Immunology. 2013 Nov;140(3):344-51. doi: 10.1111/imm.12146.