Intraarticular injections with methylprednisolone acetate reduce osteoarthritic lesions in parallel with chondrocyte stromelysin synthesis in experimental osteoarthritis.
OBJECTIVE
To examine the effect of intraarticular injections of methylprednisolone acetate (MA) on osteoarthritic lesions and chondrocyte stromelysin synthesis in experimental osteoarthritis (OA).


METHODS
In 15 mongrel dogs, the anterior cruciate ligament of the right knee was sectioned by a stab wound. Eight dogs received intraarticular injections of MA (20 mg) at the time of surgery and 4 weeks later; 7 had no treatment. The dogs were killed 8 weeks after surgery. Five normal dogs were used as controls. Macroscopic evaluation of the lesions, including measurements of osteophytes and areas of surface lesions on the condyles and plateaus, was conducted, along with histologic evaluation of the severity of lesions. Immunohistochemical analysis was carried out using a rabbit polyclonal antibody against stromelysin, followed by evaluation of matrix and chondrocyte staining using morphometric analysis.


RESULTS
Treatment with MA significantly reduced the incidence (P < 0.0004) and size (P < 0.0001) of osteophytes. The histologic grading of cartilage lesions was also significantly reduced both on condyles (P < 0.01) and on plateaus (P < 0.002). Immunohistochemical studies revealed, for OA cartilage, a marked increase (P < 0.002) in the percentage of chondrocytes positive for stromelysin and in the intensity of staining throughout all the layers of the cartilage, as well as specific matrix staining (P < 0.005). Treatment with MA reduced staining at both the chondrocyte (P < 0.002) and the matrix (P < 0.01) levels toward normal.


CONCLUSIONS
These findings provide additional evidence for the protective effect of corticosteroid injections on OA lesions, and indicate that the effect of this drug may be mediated through the suppression of stromelysin synthesis.
Pelletier
J P
JP
Department of Medicine, University of Montreal, Québec, Canada.
Mineau
F
F
Raynauld
J P
JP
Woessner
J F
JF
Gunja-Smith
Z
Z
Martel-Pelletier
J
J
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004285:Dogs; D007150:Immunohistochemistry; D007270:Injections, Intra-Articular; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D008775:Methylprednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077555:Methylprednisolone Acetate; D010003:Osteoarthritis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
D000077555:Methylprednisolone Acetate; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D008775:Methylprednisolone