Mudgett J S, Hutchinson N I, Chartrain N A, Forsyth A J, McDonnell J, Singer I I, Bayne E K, Flanagan J, Kawka D, Shen C F, Stevens K, Chen H, Trumbauer M, Visco D M
Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Arthritis Rheum. 1998 Jan;41(1):110-21. doi: 10.1002/1529-0131(199801)41:1<110::AID-ART14>3.0.CO;2-G.
It has long been proposed that stromelysin is one of the major degradative matrix metalloproteinases responsible for the loss of cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA). This hypothesis was tested by examining the arthritic paws of stromelysin 1 (SLN1)-deficient mice for loss of cartilage and for generation of neoepitopes that would be indicative of aggrecan cleavage.
The SLN1 gene was inactivated in murine embryonic stem cells, and knockout mice deficient in SLN1 activity were bred onto the B10.RIII background. The incidence and severity of collagen-induced arthritis (CIA) were compared in wild-type and knockout mice. Paws from mice with CIA were examined for loss of cartilage and for proteoglycan staining, as well as for the generation of the neoepitope FVDIPEN341.
SLN1-deficient mice developed CIA, as did the wild-type N2 mice. Histologic analyses demonstrated no significant differences among the B10.RIII, wild-type, and knockout mice in loss of articular cartilage and proteoglycan staining. No decrease in the FVDIPEN341 epitope was observed in the SLN1-deficient mice.
Disruption of the SLN1 gene neither prevents nor reduces the cartilage destruction associated with CIA. Moreover, SLN1 depletion does not prevent the cleavage of the aggrecan Asn341-Phe342 bond.
长期以来，人们一直认为基质溶解素是类风湿性关节炎（RA）和骨关节炎（OA）中导致软骨丧失的主要降解性基质金属蛋白酶之一。通过检查基质溶解素1（SLN1）缺陷小鼠的关节炎爪子是否存在软骨丧失以及是否产生可指示蛋白聚糖裂解的新表位，对这一假说进行了验证。
在小鼠胚胎干细胞中使SLN1基因失活，并将缺乏SLN1活性的基因敲除小鼠培育到B10.RIII背景中。比较野生型和基因敲除小鼠中胶原诱导性关节炎（CIA）的发病率和严重程度。检查患CIA小鼠的爪子是否存在软骨丧失和蛋白聚糖染色情况，以及新表位FVDIPEN341的产生情况。
SLN1缺陷小鼠与野生型N2小鼠一样患上了CIA。组织学分析表明，B10.RIII小鼠、野生型小鼠和基因敲除小鼠在关节软骨丧失和蛋白聚糖染色方面没有显著差异。在SLN1缺陷小鼠中未观察到FVDIPEN341表位减少。
SLN1基因的破坏既不能预防也不能减少与CIA相关的软骨破坏。此外，SLN1的缺失并不能阻止蛋白聚糖天冬酰胺341-苯丙氨酸342键的裂解。
