title: Interleukin-1 and tumor necrosis factor-alpha induce collagenolysis and bone resorption by regulation of matrix metalloproteinase-2 in mouse calvarial bone cells.
abstract: Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) greatly induces osteoclast formation and stimulates bone resorption of mouse calvaria in culture. We examined the effects of the two cytokines on the collagenolysis and bone resorption by induction of matrix metalloproteinases (MMPs). The cells were analyzed using zymographic analysis. It was shown that the mouse calvarial osteoblasts constitutively synthesize progelatinase-A (MMP-2). Interleukin-1beta markedly enhanced the messenger RNAs (mRNAs) expression of MMP-2 (gelatinase A), but slightly MMP-9 (gelatinase B), which associated with increases in bone matrix degradation. Both pro- and active-forms of MMP-2 were detected in the conditioned medium collected from calvarial cultures, and IL-1beta markedly stimulated both pro- and active-forms of the MMP-2. The expression of MMP-2 mRNAs could be detected, and they were markedly enhanced by IL-1beta on days 1 and 2. These results demonstrate that the potency of induction of MMP-2 by IL-1beta and TNF-alpha is closely linked to the respective bone-resorbing activity, suggesting that MMP-2-dependent degradation of bone matrix plays a key role in bone resorption induced by these cytokines. On the other hand, when the mouse osteoblasts were stimulated with parathyroid hormone, 1,25(OH)2D3, mononuclear cell conditioned medium (MCM) and IL-1 as bone resorption agents, collagenolysis was increased by producing the active gelatinase. Interleukin-1 in stimulating bone resorption was examined using fetal mouse long bone organ culture. Interleukin-1 stimulated bone resorption and produced marked resorption when present simultaneously. Furthermore, treatment of indomethacin and dexamethasone clearly abolished the responses of IL-1alpha and IL-1beta.
authors.affiliation: National Research Laboratory for Glycobiology, and Department of Biochemistry and Oriental Medicine, Dongguk University COM, Kyungju, Korea.
authors.forename: Bong-Seok
authors.initials: BS
authors.lastname: Kang
authors.forename: Young-Guk
authors.initials: YG
authors.lastname: Park
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Cho
authors.forename: June-Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: Tae-Kyun
authors.initials: TK
authors.lastname: Lee
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Yeun-Hwa
authors.initials: YH
authors.lastname: Gu
authors.forename: Ikukatsu
authors.initials: I
authors.lastname: Suzuki
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000201:enzymology / Q000378:metabolism*; D002117:Calcitriol / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D012886:Skull / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D024042:Collagen Type I; D007375:Interleukin-1; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D005780:Gelatin; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D002117:Calcitriol; D002118:Calcium; D007213:Indomethacin