The in vivo effects of intraarticular corticosteroid injections on cartilage lesions, stromelysin, interleukin-1, and oncogene protein synthesis in experimental osteoarthritis.
BACKGROUND
Osteoarthritis (OA) is characterized by a progressive erosion of the articular cartilage. Studies suggest that cytokines and metalloproteases play an important role in this process. Previously, we found that corticosteroids given prophylactically reduce the severity of cartilage lesions. In this study, we examined and compared the in vivo efficacy of a corticosteroid, triamcinolone hexacetonide (TH), administered either prophylactically or therapeutically, on OA lesions and on cartilage metalloproteases, interleukin-1 beta (IL-1 beta), and oncogene synthesis in experimental OA.


METHODS
This study examines the effect of intraarticular injections of TH on the progression of lesions in the experimental dog model of OA. The animals had the anterior cruciate ligament of the right knee sectioned and were killed 12 weeks after surgery. A total of 30 dogs were used in four groups: group 1 (n = 8) had no treatment; group 2 (n = 8; TH-3) received TH at time of surgery and at 4 and 8 weeks later; group 3 (n = 7; TH-2) received TH at 4 and 8 weeks after surgery; and group 4 (n = 7; TH-1) received TH at 8 weeks after surgery. Knee cartilage was submitted to macroscopic and microscopic examinations, as well as immunohistochemical studies for stromelysin, IL-1 beta, and oncoproteins, c-Fos and c-Myc.


RESULTS
Injections with TH significantly reduced the size of osteophytes in dogs from groups TH-3 (p < 0.0001) and TH-2 (p < 0.0002). The histologic severity of cartilage lesions was significantly reduced on condyles in all TH groups and on plateaus of dogs from groups TH-3 and TH-2. Immunohistochemistry revealed that TH significantly reduced the percentage of immunoreactive chondrocytes for stromelysin, and the effect was proportional to the number of injections received. For c-fos and c-myc, the reduction was particularly significant in the TH-3 and TH-2 groups. For IL-1 beta, the reduction was significant only in the TH-3 group.


CONCLUSIONS
This study provides novel data showing the protective effect of corticosteroid injections on OA cartilage lesions not only under prophylactic but also under therapeutic conditions. The effect of TH may be mediated through a direct reduction in the expression and synthesis of proteolytic enzymes, such as stromelysin. Alternatively, the steroid could act by inhibiting the stimulation of protease synthesis by cytokines/oncogenes (IL-1 beta, c-Fos, and c-Myc).
Pelletier
J P
JP
Rheumatic Disease Unit, University of Montreal, L-C. Simard Research Center, Notre-Dame Hospital, Canada.
DiBattista
J A
JA
Raynauld
J P
JP
Wilhelm
S
S
Martel-Pelletier
J
J
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D007124:Immunoenzyme Techniques; D007270:Injections, Intra-Articular; D007375:Interleukin-1 / Q000096:biosynthesis*; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis
D000305:Adrenal Cortex Hormones; D007375:Interleukin-1; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3