PMID- 21928379 OWN - NLM STAT- MEDLINE DCOM- 20120327 LR - 20191210 IS - 1554-527X (Electronic) IS - 0736-0266 (Linking) VI - 30 IP - 4 DP - 2012 Apr TI - Age-related expression of MCP-1 and MMP-3 in mouse intervertebral disc in relation to TWEAK and TNF-alpha stimulation. PG - 599-605 LID - 10.1002/jor.21560 [doi] AB - This study was undertaken to investigate the age-related differences of monocyte chemotactic protein-1 (MCP-1) and matrix metalloproteinase-3 (MMP-3) expression in mouse intervertebral disc (IVD) and to determine whether MMP-3 plays a role in disc degeneration. Expression of MCP-1 and MMP-3 mRNA in mouse IVD was assessed by quantitative PCR. The ability of MCP-1 and MMP-3 expression in IVD to respond to TNF-alpha or TWEAK stimulation was examined by quantitative PCR, WB, ELISA, and immunohistochemistry. IVD derived from MMP-3-deficient and wild-type mice were compared using Safranin-O staining and immunohistochemistry. mRNA levels of MCP-1 and MMP-3 in IVD significantly diminished and the ability of MCP-1 or MMP-3 expression to respond to TNF-alpha or TWEAK stimulation was significantly reduced as age increased. IVD derived from 64-week-old wild-type mice showed clearly diffuse proteoglycan loss by Safranin-O staining and immunohistochemistry compared with younger mice. However, no loss of proteoglycan and typeII collagen were observed in IVD derived from 64-week-old MMP-3-deficient mice. MCP-1 and MMP-3 expression in mouse IVD showed age-related decreases. The response to inflammation in IVD also displayed age-related changes. Therefore, disc degeneration may vary with the patients' age and targeting MMP-3 may be a possible future therapeutic strategy for disc degeneration. CI - Copyright (c) 2011 Orthopaedic Research Society. FAU - Fujita, Koji AU - Fujita K AD - Department of Orthopaedic Surgery, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan. FAU - Ando, Takashi AU - Ando T FAU - Ohba, Tetsuro AU - Ohba T FAU - Wako, Masanori AU - Wako M FAU - Sato, Nobutaka AU - Sato N FAU - Nakamura, Yuki AU - Nakamura Y FAU - Ohnuma, Yuko AU - Ohnuma Y FAU - Hara, Yasushi AU - Hara Y FAU - Kato, Ryohei AU - Kato R FAU - Nakao, Atsuhito AU - Nakao A FAU - Haro, Hirotaka AU - Haro H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110916 PL - United States TA - J Orthop Res JT - Journal of orthopaedic research : official publication of the Orthopaedic Research Society JID - 8404726 RN - 0 (Acan protein, mouse) RN - 0 (Aggrecans) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Cytokine TWEAK) RN - 0 (Proteoglycans) RN - 0 (Recombinant Proteins) RN - 0 (Tnfsf12 protein, mouse) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Tumor Necrosis Factors) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (vascular endothelial growth factor A, mouse) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.17 (Mmp3 protein, mouse) SB - IM MH - Aggrecans/genetics/immunology/metabolism MH - Aging/pathology/*physiology MH - Animals MH - Chemokine CCL2/*genetics/immunology/metabolism MH - Cytokine TWEAK MH - Gene Expression/drug effects/immunology MH - Intervertebral Disc/immunology/metabolism/pathology MH - Intervertebral Disc Degeneration/immunology/metabolism/*physiopathology MH - Matrix Metalloproteinase 3/*genetics/immunology/metabolism MH - Mice MH - Mice, 129 Strain MH - Mice, Inbred C57BL MH - Mice, Mutant Strains MH - Proteoglycans/biosynthesis MH - Recombinant Proteins/pharmacology MH - Tumor Necrosis Factor-alpha/*pharmacology MH - Tumor Necrosis Factors/*pharmacology MH - Vascular Endothelial Growth Factor A/genetics EDAT- 2011/09/20 06:00 MHDA- 2012/03/28 06:00 CRDT- 2011/09/20 06:00 PHST- 2011/03/12 00:00 [received] PHST- 2011/08/30 00:00 [accepted] PHST- 2011/09/20 06:00 [entrez] PHST- 2011/09/20 06:00 [pubmed] PHST- 2012/03/28 06:00 [medline] AID - 10.1002/jor.21560 [doi] PST - ppublish SO - J Orthop Res. 2012 Apr;30(4):599-605. doi: 10.1002/jor.21560. Epub 2011 Sep 16.