Pelletier J P, Mineau F, Raynauld J P, Woessner J F, Gunja-Smith Z, Martel-Pelletier J
Department of Medicine, University of Montreal, Québec, Canada.
Arthritis Rheum. 1994 Mar;37(3):414-23. doi: 10.1002/art.1780370316.
To examine the effect of intraarticular injections of methylprednisolone acetate (MA) on osteoarthritic lesions and chondrocyte stromelysin synthesis in experimental osteoarthritis (OA).
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.
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.
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.
研究关节内注射醋酸甲泼尼龙(MA)对实验性骨关节炎(OA)骨关节炎性病变及软骨细胞基质溶解素合成的影响。
选取15只杂种犬,通过刺伤切断右膝前交叉韧带。8只犬在手术时及术后4周接受关节内注射MA(20mg);7只未接受治疗。术后8周处死这些犬。选取5只正常犬作为对照。对病变进行宏观评估,包括测量骨赘以及髁和平台表面病变的面积,同时对病变严重程度进行组织学评估。使用抗基质溶解素兔多克隆抗体进行免疫组织化学分析,随后采用形态计量分析评估基质和软骨细胞染色情况。
MA治疗显著降低了骨赘的发生率(P<0.0004)和大小(P<0.0001)。髁和平台软骨病变的组织学分级也显著降低(髁,P<0.01;平台,P<0.002)。免疫组织化学研究显示,对于OA软骨,基质溶解素阳性软骨细胞的百分比以及软骨各层的染色强度均显著增加(P<0.002),同时伴有特异性基质染色(P<0.005)。MA治疗使软骨细胞(P<0.002)和基质(P<0.01)水平的染色恢复至正常。
这些发现为皮质类固醇注射对OA病变的保护作用提供了更多证据,并表明该药物的作用可能是通过抑制基质溶解素合成介导的。