title: Age-related expression of MCP-1 and MMP-3 in mouse intervertebral disc in relation to TWEAK and TNF-α stimulation.
abstract: 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-α 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-α 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.
authors.affiliation: Department of Orthopaedic Surgery, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Takashi
authors.initials: T
authors.lastname: Ando
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohba
authors.forename: Masanori
authors.initials: M
authors.lastname: Wako
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Sato
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohnuma
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hara
authors.forename: Ryohei
authors.initials: R
authors.lastname: Kato
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Nakao
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Haro
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000074049:Cytokine TWEAK; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007403:Intervertebral Disc / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011509:Proteoglycans / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048069:Tumor Necrosis Factors / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C508320:Acan protein, mouse; D053674:Aggrecans; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D000074049:Cytokine TWEAK; D011509:Proteoglycans; D011994:Recombinant Proteins; C491645:Tnfsf12 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse