RRC ID 41462
著者 Onodera S, Nishihira J, Iwabuchi K, Koyama Y, Yoshida K, Tanaka S, Minami A.
タイトル Macrophage migration inhibitory factor up-regulates matrix metalloproteinase-9 and -13 in rat osteoblasts. Relevance to intracellular signaling pathways.
ジャーナル J Biol Chem
Abstract Neutral matrix metalloproteinases (MMPs) play an important role in bone matrix degradation accompanied by bone remodeling. We herein show for the first time that macrophage migration inhibitory factor (MIF) up-regulates MMP-13 (collagenase-3) mRNA of rat calvaria-derived osteoblasts. The mRNA up-regulation was seen at 3 h in response to MIF (10 microg/ml), reached the maximum level at 6-12 h, and returned to the basal level at 36 h. MMP-13 mRNA up-regulation was preceded by up-regulation of c-jun and c-fos mRNA. Tissue inhibitor of metalloproteinase (TIMP)-1 and MMP-9 (92-kDa type IV collagenase) were also up-regulated, but to a lesser extent. The MMP-13 mRNA up-regulation was significantly suppressed by genistein, herbimycin A and 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine. Similarly, a selective mitogen-activated protein kinase (MAPK) kinase (MEK)1/2 inhibitor (PD98059) and c-jun/activator protein (AP)-1 inhibitor (curcumin) suppressed MMP-13 mRNA up-regulation induced by MIF. The mRNA levels of c-jun and c-fos in response to MIF were also inhibited by PD98059. Consistent with these results, MIF stimulated phosphorylation of tyrosine, autophosphorylation of Src, activation of Ras, activation of extracellular signal-regulated kinases (ERK) 1/2, a MAPK, but not c-Jun N-terminal kinase or p38, and phosphorylation of c-Jun. Osteoblasts obtained from calvariae of newborn JunAA mice, defective in phosphorylation of c-Jun, or newborn c-Fos knockout (Fos -/- ) mice, showed much less induction of MMP-13 with the addition of MIF than osteoblasts obtained from wild-type or littermate control mice. Taken together, these results suggest that MIF increases the MMP-13 mRNA level of rat osteoblasts via the Src-related tyrosine kinase-, Ras-, ERK1/2-, and AP-1-dependent pathway.
巻・号 277(10)
ページ 7865-74
公開日 2002-3-8
DOI 10.1074/jbc.M106020200
PII S0021-9258(19)36377-X
PMID 11751895
MeSH Animals Bone and Bones / metabolism Collagenases / biosynthesis* Collagenases / metabolism Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Fibroblasts / enzymology Fibroblasts / metabolism Flavonoids / pharmacology Genes, Dominant MAP Kinase Kinase 1 MAP Kinase Kinase 2 Macrophage Migration-Inhibitory Factors / metabolism* Matrix Metalloproteinase 13 Matrix Metalloproteinase 9 / biosynthesis* Mitogen-Activated Protein Kinase Kinases / metabolism Mitogen-Activated Protein Kinases / metabolism Osteoblasts / enzymology* Osteoblasts / metabolism* Phosphorylation Protein Binding Protein Serine-Threonine Kinases / metabolism Protein-Tyrosine Kinases / metabolism Proto-Oncogene Proteins c-jun / metabolism RNA, Messenger / metabolism Rats Recombinant Proteins / metabolism Signal Transduction* Time Factors Transcription Factor AP-1 / metabolism Tyrosine / metabolism Up-Regulation* p38 Mitogen-Activated Protein Kinases src-Family Kinases / metabolism
IF 4.238
引用数 133
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)