Spontaneous development of synovitis and cartilage degeneration in transgenic mice overexpressing cathepsin K.
OBJECTIVE
Several recent studies have demonstrated that cathepsin K, a proteolytic enzyme capable of degrading native fibrillar collagen, is overexpressed in osteoarthritic cartilage and inflamed synovial tissue. However, it is not known whether increased cathepsin K production is a primary or a secondary event in these diseases. The availability of transgenic UTU17 mice, which exhibit constitutive overexpression of the cathepsin K gene, prompted us to study possible arthritic changes in their knee joints.


METHODS
Progression of synovitis and articular cartilage degeneration in the knee joints of UTU17 mice and their nontransgenic littermates was monitored by histologic analyses at 7 and 12 months of age. Distribution of cathepsin K in the knee joints was studied by immunohistochemistry.


RESULTS
At the age of 7 months, UTU17 mice exhibited clear signs of synovitis, with strong immunostaining for cathepsin K in the synovial lining and the stroma, while control knee joints appeared normal. At 12 months, marked synovial thickening and fibrosis and severe degradation of cartilage and subchondral bone were observed in UTU17 mouse knee joints. In areas of cartilage degeneration, both chondrocytes and cells of hypertrophic synovia were positive for cathepsin K. At 12 months, synovia of control mice revealed only a few isolated cathepsin K-positive cells and mild changes in articular cartilage.


CONCLUSIONS
Our findings demonstrate that overexpression of the cathepsin K gene under its own promoter in transgenic mice makes them susceptible to progressive synovitis, which, upon aging, results in synovial hyperplasia and fibrosis and subsequent destruction of articular cartilage and bone.
Morko
Jukka
J
University of Turku, Turku, Finland.
Kiviranta
Riku
R
Joronen
Kirsi
K
Säämänen
Anna-Marja
AM
Vuorio
Eero
E
Salminen-Mankonen
Heli
H
D000375:Aging / Q000473:pathology; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D007150:Immunohistochemistry; D007719:Knee Joint / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011401:Promoter Regions, Genetic; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D013585:Synovitis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*
D002403:Cathepsins; D056657:Cathepsin K; C534132:Ctsk protein, mouse