Myers S L, O'Connor B L, Brandt K D
Rheumatology Division, Indiana University School of Medicine, Indiana University Multipurpose Arthritis and Musculoskeletal Diseases Center, Indianapolis, USA.
J Rheumatol. 1996 Oct;23(10):1744-8.
The magnitude of articular cartilage destruction or repair in osteoarthritic (OA) joints has been deduced in some studies from the synovial fluid (SF) concentration of proteins derived from the extracellular matrix of the cartilage, without regard to the low grade synovitis that is often present in this disease. We examined the clearance kinetics of albumin, as a surrogate for cartilage derived proteins, from OA and control joints in an established canine model.
Twelve weeks after the left anterior cruciate ligament of 6 normal dogs was transected, 131I albumin (RISA) was injected into the contralateral (control) knee. Surface radioactivity was monitored for 7 h, and SF was then aspirated to determine the SF RISA concentration and leukocyte count, and calculate the volume of distribution (VD) and clearance of RISA. One week later, RISA was injected into the cruciate deficient knee and these measurements were repeated, then the intensity of synovial inflammation and severity of cartilage changes of OA in both knees were assessed.
Synovitis and articular cartilage ulceration were seen only in the cruciate-deficient OA knee, in which the mean SF leukocyte count (1570/mm3), thickness of the synovial intima (mean = 30 microns), and severity of synovial mononuclear cell infiltration (mean = 13,500 cells/mm2) significantly exceeded those in the contralateral knee (850/mm3, 13 microns, 1400 cells/mm2; p < or = 0.01 in each case). In each dog, RISA VD in the OA knee was higher than in the contralateral knee (mean = 9.2 +/- 3.6 and 3.7 +/- 0.9 ml, respectively; p = 0.008) and RISA clearance rate in the OA knee exceeded that in the contralateral knee (3.8 +/- 1.5 and 1.4 +/- 0.3 microliters/min, respectively; p = 0.009).
Accelerated clearance of protein from the OA joint with low grade synovitis could significantly affect the SF concentration of cartilage derived proteins. Therefore, inferences about the effect of a therapeutic agent on cartilage metabolism based upon changes in the concentration of a protein in serial samples of OA SF may be misleading unless protein clearance kinetics have been determined.
在一些研究中，已根据源自软骨细胞外基质的蛋白质在滑液（SF）中的浓度推断骨关节炎（OA）关节中关节软骨破坏或修复的程度，而未考虑该疾病中常存在的轻度滑膜炎。我们在一个成熟的犬类模型中研究了白蛋白作为软骨衍生蛋白的替代物从OA关节和对照关节的清除动力学。
6只正常犬的左前交叉韧带横断12周后，将131I白蛋白（人血清白蛋白放射性碘标记物）注入对侧（对照）膝关节。监测表面放射性7小时，然后抽取滑液以测定滑液中131I白蛋白的浓度和白细胞计数，并计算分布容积（VD）和131I白蛋白的清除率。一周后，将131I白蛋白注入交叉韧带缺损的膝关节并重复这些测量，然后评估双膝OA的滑膜炎强度和软骨变化严重程度。
滑膜炎和关节软骨溃疡仅见于交叉韧带缺损的OA膝关节，其中滑液平均白细胞计数（1570/mm3）、滑膜内膜厚度（平均=30微米）和滑膜单核细胞浸润严重程度（平均=13500个细胞/mm2）显著超过对侧膝关节（850/mm3、13微米、1400个细胞/mm2；每种情况p≤0.01）。在每只犬中，OA膝关节中的131I白蛋白分布容积高于对侧膝关节（分别平均为9.2±3.6和3.7±0.9 ml；p = 0.008），且OA膝关节中131I白蛋白的清除率超过对侧膝关节（分别为3.8±1.5和1.4±0.3微升/分钟；p = 0.009）。
伴有轻度滑膜炎的OA关节中蛋白质清除加速可能会显著影响软骨衍生蛋白的滑液浓度。因此，基于OA滑液系列样本中蛋白质浓度变化推断治疗剂对软骨代谢的影响可能会产生误导，除非已确定蛋白质清除动力学。
