A type XI collagen mutation leads to increased degradation of type II collagen in articular cartilage.
OBJECTIVE
To determine in articular cartilage whether degraded type II collagen is more abundant in Col11a1 mutant cho/+ than in age-matched +/+ mice and whether collagen degradation occurs in a generalized or localized fashion.


METHODS
Knee joints from cho/+ and +/+ mice at 6, 9, 12 and 15 months of age were dissected, fixed, cryosectioned, and stained with antibody COL2-3/4m against denatured type II collagen using a FITC-conjugated secondary antibody. Sections were viewed and photographed under a fluorescence microscope and areas of staining were quantified.


RESULTS
Before 12 months of age, little degraded collagen staining was detectable in +/+ or cho/+ mice. By 15 months, however, cho/+ mice showed significantly more degraded type II collagen than age-matched controls. Degraded collagen staining was localized at the articular surface, not distributed generally throughout the articular cartilage.


CONCLUSIONS
The results suggest a model in which cumulative biomechanical stresses trigger increased collagen synthesis and degradation in both +/+ and cho/+ mice at around 12 months of age. Cho/+ mice, however, are less able to synthesize and assemble normal replacement collagen fibrils because of the Col11a1 mutation. Degradation is further activated, resulting in the accumulation of degraded type II collagen in the articular cartilage extracellular matrix. Similar mutations that do not overtly affect skeletal development may likewise predispose humans to increased collagen degradation and resultant osteoarthritis.
Rodriguez
R R
RR
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah 84602, USA.
Seegmiller
R E
RE
Stark
M R
MR
Bridgewater
L C
LC
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000503:physiopathology*; D024043:Collagen Type II / Q000378:metabolism*; D024161:Collagen Type XI / Q000235:genetics*; D006614:Hindlimb; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence / Q000379:methods; D009154:Mutation; D010003:Osteoarthritis / Q000503:physiopathology*; D011489:Protein Denaturation
D024043:Collagen Type II; D024161:Collagen Type XI