PMID- 16574073 OWN - NLM STAT- MEDLINE DCOM- 20060524 LR - 20061115 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 343 IP - 3 DP - 2006 May 12 TI - Mu-calpain is involved in the regulation of TNF-alpha-induced matrix metalloproteinase-3 release in a rheumatoid synovial cell line. PG - 937-42 AB - Calpain is secreted by intra-articular synovial cells and degrades the main components of cartilage matrix proteins, proteoglycan, and collagen, causing cartilage destruction. Matrix metalloproteinase-3 (MMP-3) has also been detected in synovial fluid and serum, and is involved in the development and progression of rheumatoid arthritis by degradation of the extracellular matrix and cartilage destruction. To investigate the relationship between calpain and MMP-3 in rheumatic inflammation, we utilized the rheumatic synovial cell line, MH7A. Tumor necrosis factor (TNF-alpha) stimulation-induced increased expression of mu-calpain, m-calpain, and MMP-3 in these cells, as well as the release of calpain and MMP-3 into the culture medium. The calpain inhibitors, ALLN (calpain inhibitor I) and calpeptin, did not affect the intracellular expression of MMP-3, but reduced the secretion of MMP-3 in a concentration-dependent manner. Down-regulation of mu- but not m-calpain by small interfering RNAs abolished TNF-alpha-induced MMP-3 release from the synovial cells. These findings suggest that calpain, particularly mu-calpain, regulates MMP-3 release by rheumatic synovial cells, in addition to exerting its own degradative action on cartilage. FAU - Morita, Masaji AU - Morita M AD - Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. FAU - Banno, Yoshiko AU - Banno Y FAU - Dohjima, Taikoh AU - Dohjima T FAU - Nozawa, Satoshi AU - Nozawa S FAU - Fushimi, Kazunari AU - Fushimi K FAU - Fan, De-Gang AU - Fan DG FAU - Ohno, Takatoshi AU - Ohno T FAU - Miyazawa, Keiji AU - Miyazawa K FAU - Liu, Naxin AU - Liu N FAU - Shimizu, Katsuji AU - Shimizu K LA - eng PT - Journal Article DEP - 20060309 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Cysteine Proteinase Inhibitors) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.22.- (Calpain) RN - EC 3.4.22.- (m-calpain) RN - EC 3.4.22.- (mu-calpain) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Arthritis, Rheumatoid/*enzymology MH - Calpain/antagonists & inhibitors/biosynthesis/*physiology MH - Cell Line MH - Cysteine Proteinase Inhibitors/pharmacology MH - Humans MH - Matrix Metalloproteinase 3/*biosynthesis MH - RNA Interference MH - Synovial Membrane/cytology/*enzymology MH - Tumor Necrosis Factor-alpha/*pharmacology MH - Up-Regulation EDAT- 2006/04/01 09:00 MHDA- 2006/05/25 09:00 CRDT- 2006/04/01 09:00 PHST- 2006/02/03 00:00 [received] PHST- 2006/02/27 00:00 [accepted] PHST- 2006/04/01 09:00 [pubmed] PHST- 2006/05/25 09:00 [medline] PHST- 2006/04/01 09:00 [entrez] AID - S0006-291X(06)00466-9 [pii] AID - 10.1016/j.bbrc.2006.02.155 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2006 May 12;343(3):937-42. doi: 10.1016/j.bbrc.2006.02.155. Epub 2006 Mar 9.