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. CONCLUSION 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.

[1]  J. Pelletier,et al.  Coordinate synthesis of stromelysin, interleukin-1, and oncogene proteins in experimental osteoarthritis. An immunohistochemical study. , 1993, The American journal of pathology.

[2]  K. Iwata,et al.  Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium. , 1992, Laboratory investigation; a journal of technical methods and pathology.

[3]  N. Bhardwaj,et al.  Detection of stromelysin and collagenase in synovial fluid from patients with rheumatoid arthritis and posttraumatic knee injury. , 1992, Arthritis and rheumatism.

[4]  K. Brandt,et al.  Osteoarthritic changes in canine articular cartilage, subchondral bone, and synovium fifty-four months after transection of the anterior cruciate ligament. , 2010, Arthritis and rheumatism.

[5]  G. Firestein,et al.  Gene expression (collagenase, tissue inhibitor of metalloproteinases, complement, and HLA-DR) in rheumatoid arthritis and osteoarthritis synovium. Quantitative analysis and effect of intraarticular corticosteroids. , 1991, Arthritis and rheumatism.

[6]  D. Dean Proteinase-mediated cartilage degradation in osteoarthritis. , 1991, Seminars in arthritis and rheumatism.

[7]  J. Pelletier,et al.  Are cytokines involved in osteoarthritic pathophysiology? , 1991, Seminars in Arthritis & Rheumatism.

[8]  A. Freemont,et al.  Demonstration of variation in chondrocyte activity in different zones of articular cartilage: an assessment of the value of in-situ hybridization. , 1991, International journal of experimental pathology.

[9]  J. Pelletier,et al.  Synovial membrane histology and immunopathology in rheumatoid arthritis and osteoarthritis. In vivo effects of antirheumatic drugs. , 1991, Arthritis and rheumatism.

[10]  J. Martel-Pelletier,et al.  Imbalance between the mechanisms of activation and inhibition of metalloproteases in the early lesions of experimental osteoarthritis. , 1990, Arthritis and rheumatism.

[11]  K. Brandt,et al.  Synovitis and osteoarthritic changes in canine articular cartilage after anterior cruciate ligament transection. Effect of surgical hemostasis. , 1990, Arthritis and rheumatism.

[12]  R. Altman,et al.  Therapeutic treatment of canine osteoarthritis with glycosaminoglycan polysulfuric acid ester. , 1989, Arthritis and rheumatism.

[13]  J. Pelletier,et al.  In vitro effects of tiaprofenic acid, sodium salicylate and hydrocortisone on the proteoglycan metabolism of human osteoarthritic cartilage. , 1989, The Journal of rheumatology.

[14]  P. Ghosh Therapeutic modulation of cartilage catabolism by nonsteroidal antiinflammatory drugs in arthritis. , 1989, Seminars in arthritis and rheumatism.

[15]  J. Pelletier,et al.  Protective effects of corticosteroids on cartilage lesions and osteophyte formation in the Pond-Nuki dog model of osteoarthritis. , 1989, Arthritis and rheumatism.

[16]  R. Mize,et al.  Quantitative immunocytochemistry using an image analyzer. II. Concentration standards for transmitter immunocytochemistry , 1988, Journal of Neuroscience Methods.

[17]  A. Tsou,et al.  Glucocorticoids selectively inhibit the transcription of the interleukin 1 beta gene and decrease the stability of interleukin 1 beta mRNA. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[18]  J. Pelletier,et al.  Proteoglycan-degrading acid metalloprotease activity in human osteoarthritic cartilage, and the effect of intraarticular steroid injections. , 1987, Arthritis and rheumatism.

[19]  K. von der Mark,et al.  Dexamethasone impairs growth and collagen synthesis in condylar cartilage in vitro. , 1987, Bone and mineral.

[20]  K. Brandt,et al.  Triamcinolone hexacetonide protects against fibrillation and osteophyte formation following chemically induced articular cartilage damage. , 1985, Arthritis and rheumatism.

[21]  B. Steinetz,et al.  A new model of osteoarthritis in rabbits. III. Evaluation of anti-osteoarthritic effects of selected drugs administered intraarticularly. , 1983, Arthritis and rheumatism.

[22]  D. Hill Effects of cortisol on cell proliferation and proteoglycan synthesis and degradation in cartilage zones of the calf costochondral growth plate in vitro with and without rat plasma somatomedin activity. , 1981, The Journal of endocrinology.

[23]  F. Behrens,et al.  Alterations of rabbit articular cartilage by intra-articular injections of glucocorticoids. , 1975, The Journal of bone and joint surgery. American volume.

[24]  H. Dorfman,et al.  Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. , 1971, The Journal of bone and joint surgery. American volume.

[25]  R. Moskowitz,et al.  Experimentally induced corticosteroid arthropathy. , 1970, Arthritis and rheumatism.

[26]  R. Salter,et al.  Hydrocortisone arthropathy--an experimental investigation. , 1967, Canadian Medical Association journal.