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: Bong-Seok Kang, Young-Guk Park, Jin-Young Cho, June-Ki Kim, Tae-Kyun Lee, Dong-Wook Kim, Yeun-Hwa Gu, Ikukatsu Suzuki, Young-Chae Chang, Cheorl-Ho Kim
• Journal: Immunopharmacology and immunotoxicology (Immunopharmacol Immunotoxicol) Vol. 25 Issue 3 Pg. 347-64 (Aug 2003) ISSN: 0892-3973 [Print] England
• PMID: 19180798 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Collagen Type I
• Interleukin-1
• Interleukin-1alpha
• Interleukin-1beta
• RNA, Messenger
• Recombinant Proteins
• Tumor Necrosis Factor-alpha
• Dexamethasone
• Gelatin
• Matrix Metalloproteinase 2
• Mmp2 protein, mouse
• Matrix Metalloproteinase 9
• Mmp9 protein, mouse
• Calcitriol
• Calcium
• Indomethacin

Topics

• Animals
• Animals, Newborn
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Bone Remodeling (drug effects)
• Bone Resorption (enzymology, metabolism)
• Calcitriol (metabolism)
• Calcium (metabolism)
• Cells, Cultured
• Collagen Type I (metabolism)
• Dexamethasone (pharmacology)
• Enzyme Induction
• Gelatin (metabolism)
• Humans
• Indomethacin (pharmacology)
• Interleukin-1 (metabolism)
• Interleukin-1alpha (metabolism)
• Interleukin-1beta (metabolism)
• Matrix Metalloproteinase 2 (biosynthesis, genetics)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Mice, Inbred BALB C
• Osteoblasts (drug effects, enzymology, immunology, metabolism)
• RNA, Messenger (biosynthesis)
• Recombinant Proteins (metabolism)
• Skull (drug effects, enzymology, immunology, metabolism)
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)