Fernandes J C, Martel-Pelletier J, Lascau-Coman V, Moldovan F, Jovanovic D, Raynauld J P, Pelletier J P
Osteoarthritis Research Unit, Centre de recherche Louis-Charles Simard, Centre hospitalier de l'Université de Montréal, Québec, Canada.
J Rheumatol. 1998 Aug;25(8):1585-94.
The coexistence of different collagenases in cartilage suggests the possibility of specific roles for these enzymes in the degradation of the collagen network in osteoarthritis (OA). We investigated the in situ synthesis and distribution of collagenase- and collegenase-3 in normal and early experimental OA cartilage.
The OA model was created on 12 mongrel dogs by sectioning the anterior cruciate ligament of the right stifle joint with a stab wound. Dogs were divided into 3 groups of 4 animals each, and sacrificed at 4, 8, and 12 weeks, respectively. A 4th group (n = 4) of unoperated dogs was used as control. Articular cartilage from femoral condyles and tibial plateaus was examined histologically to grade severity of lesions, and immunohistochemical and morphometric analyses were performed to detect the presence of chondrocytes producing collagenase-1 and -3.
In OA dogs, the histologic severity of lesions increased with time, being most severe at 8 and 12 weeks after surgery. In cartilage from OA compared to unoperated dogs, the immunoreactivity was 5-9 times higher (p < 0.0002) for collagenase-1, and 3-6 times higher (p < 0.0002) for collagenase-3, in both femoral condyles and tibial plateaus. Although the cell score increased throughout the cartilage, comparison of the superficial and upper intermediate layers (superficial) with the lower intermediate and deep layers (deep) revealed a significantly higher level for collagenase-1 (p < 0.007) in the superficial layers, contrary to the collagenase-3 data, which indicated a higher level (p < 0.007) in the deep layers. For collagenase- , the cell score increased steadily up to the 12th week, and for collagenase-3, the elevation peaked at 8 weeks. Correlation between the histologic severity and cell score in cartilage specimens from unoperated and OA dogs revealed the highest coefficient for collagenase- at the superficial layers (r = 0.69, p < 0.0001), while for collagenase-3, this was noted at the deep layers (r = 0.65, p < 0.0004).
The number of chondrocytes involved in the synthesis of collagenase-1 and collegenase-3 increases dramatically in the early phase of OA. However, the difference in the topographic distribution of these enzymes, as well as the variation in their correlation pattern, may reflect a different function allocated for each collagenase in the OA cartilage degradation process.
软骨中不同胶原酶的共存提示这些酶在骨关节炎（OA）胶原网络降解中可能具有特定作用。我们研究了正常和早期实验性OA软骨中胶原酶-1和胶原酶-3的原位合成及分布。
通过刺伤切断12只杂种犬右膝关节前交叉韧带建立OA模型。将犬分为3组，每组4只，分别在4周、8周和12周处死。第4组（n = 4）未手术的犬作为对照。对股骨髁和胫骨平台的关节软骨进行组织学检查以评估病变严重程度，并进行免疫组织化学和形态计量分析以检测产生胶原酶-1和-3的软骨细胞的存在。
在OA犬中，病变的组织学严重程度随时间增加，在术后8周和12周最为严重。与未手术犬相比，OA犬股骨髁和胫骨平台软骨中胶原酶-1的免疫反应性高5 - 9倍（p < 0.0002），胶原酶-3高3 - 6倍（p < 0.0002）。尽管整个软骨中的细胞评分增加，但浅层和上中层（表层）与下中层和深层（深层）相比，表层胶原酶-1水平显著更高（p < 0.007），与胶原酶-3的数据相反，后者表明深层水平更高（p < 0.007）。对于胶原酶-1，细胞评分在第12周前稳步增加，对于胶原酶-3，升高在8周达到峰值。未手术和OA犬软骨标本中组织学严重程度与细胞评分之间的相关性显示，表层胶原酶-1的系数最高（r = 0.69，p < 0.0001），而对于胶原酶-3，在深层观察到这一点（r = 0.65，p < 0.0004）。
在OA早期，参与胶原酶-1和胶原酶-3合成的软骨细胞数量显著增加。然而，这些酶在地形分布上的差异以及它们相关模式的变化，可能反映了每种胶原酶在OA软骨降解过程中分配的不同功能。
