Cartilage metalloproteases in disuse atrophy.
A canine knee model of disuse atrophy produced by nonrigid fixation (sling) was characterized in respect to variables of proteoglycan size distribution, as well as biomechanical properties versus controls. Using this model, we found, in addition to the accepted dogma attributing changes to reduced protein synthesis by chondrocytes, that there is elevation of proteases and depression of tissue inhibitor of metalloproteases (TIMP) in atrophic knee cartilage. The findings are suggestive of cartilage remodelling reminiscent of bone remodelling in disuse atrophy reported by others. Whether the abnormal changes of protease-TIMP balance in knee cartilage can be retarded prophylactically by concurrent treatment with pentosan polysulfate and insulin like growth factor 1 remains uncertain.
Grumbles
R M
RM
Veterans Affairs Medical Center, University of Miami School of Medicine, FL 33125, USA.
Howell
D S
DS
Howard
G A
GA
Roos
B A
BA
Setton
L A
LA
Mow
V C
VC
Ratcliffe
A
A
Muller
F J
FJ
Altman
R D
RD
D000818:Animals; D001284:Atrophy; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D017364:Collagenases / Q000096:biosynthesis* / Q000187:drug effects; D004285:Dogs; D004359:Drug Therapy, Combination; D006023:Glycoproteins / Q000096:biosynthesis*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000627:therapeutic use; D007719:Knee Joint; D020781:Matrix Metalloproteinase 1; D008666:Metalloendopeptidases / Q000187:drug effects / Q000378:metabolism*; D010426:Pentosan Sulfuric Polyester / Q000008:administration & dosage / Q000627:therapeutic use; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D019714:Tissue Inhibitor of Metalloproteinases; D010426:Pentosan Sulfuric Polyester; D007334:Insulin-Like Growth Factor I; D017364:Collagenases; D008666:Metalloendopeptidases; D020781:Matrix Metalloproteinase 1