title: IL-1beta suppresses the formation of osteoclasts by increasing OPG production via an autocrine mechanism involving celecoxib-related prostaglandins in chondrocytes.
abstract: Elevated interleukin (IL)-1 concentrations in synovial fluid have been implicated in joint bone and cartilage destruction. Previously, we showed that IL-1beta stimulated the expression of prostaglandin (PG) receptor EP4 via increased PGE(2) production. However, the effect of IL-1beta on osteoclast formation via chondrocytes is unclear. Therefore, we examined the effect of IL-1beta and/or celecoxib on the expression of macrophage colony-stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) in human chondrocytes, and the indirect effect of IL-1beta on osteoclast-like cell formation using RAW264.7 cells. OPG and RANKL expression increased with IL-1beta; whereas M-CSF expression decreased. Celecoxib blocked the stimulatory effect of IL-1beta. Conditioned medium from IL-1beta-treated chondrocytes decreased TRAP staining in RAW264.7 cells. These results suggest that IL-1beta suppresses the formation of osteoclast-like cells via increased OPG production and decreased M-CSF production in chondrocytes, and OPG production may increase through an autocrine mechanism involving celecoxib-related PGs.
authors.affiliation: Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Aki
authors.initials: A
authors.lastname: Namba
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Aida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Honda
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Naoto
authors.initials: N
authors.lastname: Suzuki
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsumura
authors.forename: Masao
authors.initials: M
authors.lastname: Maeno
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D001483:Base Sequence; D000068579:Celecoxib; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D017077:Culture Media, Conditioned; D017931:DNA Primers / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D053244:Osteoprotegerin / Q000096:biosynthesis* / Q000235:genetics; D011453:Prostaglandins / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D017077:Culture Media, Conditioned; D017931:DNA Primers; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D053244:Osteoprotegerin; D011453:Prostaglandins; D011720:Pyrazoles; D053245:RANK Ligand; D013449:Sulfonamides; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor; D000068579:Celecoxib; D015232:Dinoprostone