Pathogenesis of osteoarthritis-like changes in the joints of mice deficient in type IX collagen.
OBJECTIVE
To examine the pathogenetic mechanisms of osteoarthritis (OA)-like changes in Col9a1-/- mice, which are deficient in type IX collagen.


METHODS
Knee joints and temporomandibular joints (TMJs) from Col9a1-/- mice and their wild-type (Col9a1+/+) littermates were examined by light microscopy. Immunohistochemical staining was performed to examine the expression of matrix metalloproteinase 3 (MMP-3) and MMP-13, degraded type II collagen, and the discoidin domain receptor 2 (DDR-2) in knee joints. Cartilage mechanics were also evaluated for compressive properties by microindentation testing of the tibial plateau and for tensile properties by osmotic loading of the femoral condyle.


RESULTS
Histologic analysis showed age-dependent OA-like changes in the knee and TMJs of Col9a1-/- mice starting at the age of 3 months. At the age of 6 months, enhanced proteoglycan degradation was observed in the articular cartilage of the knee and TMJs of the mutant mice. The expression of MMP-13 and DDR-2 protein and the amount of degraded type II collagen were higher in the knee joints of Col9a1-/- mice than in their wild-type littermates at the age of 6 months. Changes in cartilage mechanics were observed in the femoral and tibial plateaus of Col9a1-/- mice at 6 months, including a decrease in the compressive modulus and uniaxial modulus. At 3 and 6 months of age, tibial cartilage in Col9a1-/- mice was found to be more permeable to fluid flow, with an associated compromise in the fluid pressurization mechanism of load support. All of these changes occurred only at medial sites.


CONCLUSIONS
Lack of type IX collagen in Col9a1-/- mice results in age-dependent OA-like changes in the knee joints and TMJs.
Hu
K
K
Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
Xu
L
L
Cao
L
L
Flahiff
C M
CM
Brussiau
J
J
Ho
K
K
Setton
L A
LA
Youn
I
I
Guilak
F
F
Olsen
B R
BR
Li
Y
Y
D000818:Animals; D024081:Collagen Type IX / Q000172:deficiency* / Q000235:genetics; D017364:Collagenases / Q000378:metabolism; D000070818:Discoidin Domain Receptors; D004195:Disease Models, Animal; D007596:Joints / Q000378:metabolism / Q000473:pathology*; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000235:genetics* / Q000473:pathology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011975:Receptors, Mitogen / Q000378:metabolism
D024081:Collagen Type IX; D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D019278:Matrix Metalloproteinase 3