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Age‐related expression of MCP‐1 and MMP‐3 in mouse intervertebral disc in relation to TWEAK and TNF‐α stimulation
Author(s) -
Fujita Koji,
Ando Takashi,
Ohba Tetsuro,
Wako Masanori,
Sato Nobutaka,
Nakamura Yuki,
Ohnuma Yuko,
Hara Yasushi,
Kato Ryohei,
Nakao Atsuhito,
Haro Hirotaka
Publication year - 2012
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21560
Subject(s) - intervertebral disc , immunohistochemistry , matrix metalloproteinase , stimulation , medicine , proteoglycan , pathology , inflammation , mmp3 , messenger rna , gene expression , biology , anatomy , cartilage , gene , biochemistry
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. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:599–605, 2012