Metalloproteinase and tissue inhibitor of metalloproteinase expression in the murine STR/ort model of osteoarthritis.
OBJECTIVE
To study the temporal expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in the STR/ort mouse model of osteoarthritis, using in situ hybridization with oligonucleotide probes and specific antisera for each protein.


METHODS
In situ hybridization and immunolocalization experiments were performed on serial cryosections of knee joints from STR/ort and control CBA mice. The mRNA was localized using digoxygenin-labeled probes.


RESULTS
MMP2, MMP3, MMP7, MMP9, MMP13, MT1-MMP and TIMP2 mRNA was detected in the tibial articular chondrocytes of STR/ort mice at all ages (12, 18, 24, 30 and 35 weeks). Levels were always higher than in age-matched CBA mice. Neither MMP8 nor TIMP1 mRNA was detected in murine cartilage. The location and distribution of each of the MMP mRNA transcripts varied within the tibial plateau. Immunolocalization consistently detected MMP3 and MT1-MMP in articular cartilage and MMP13 in calcified cartilage. Other proteases and their inhibitors were not detected in either of these cartilages but MMP2 and MMP9 were immunolocalized in bone marrow cells and growth cartilage respectively.


CONCLUSIONS
Expression of all the detected MMPs and TIMP-2 is up-regulated in STR/ort mice at the mRNA level. However, failure to detect protein expression for MMPs 2, 7, 9, 13 and TIMPs 1 and 2 in murine chondrocytes by immunohistochemistry indicates that the changes in mRNA levels in STR/ort mice must be interpreted with caution.
Department of Veterinary Basic Sciences, Royal Veterinary College, London NW1 0TU, UK.
J
J
Flannelly
M G
MG
Chambers
J
J
Dudhia
R M
RM
Hembry
G
G
Murphy
R M
RM
Mason
M T
MT
Bayliss
D000818:Animals; D002358:Cartilage, Articular; D019902:Chondrocytes; D017364:Collagenases / Q000235:genetics; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D017403:In Situ Hybridization; D053509:Matrix Metalloproteinase 13; D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D020784:Matrix Metalloproteinase 8 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D010003:Osteoarthritis / Q000235:genetics*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*
C507096:Mmp14 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C507081:Mmp13 protein, mouse; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14