Distal femoral intercondylar notch dimensions and their relationship to composition and metabolism of the canine anterior cruciate ligament

SummaryObjectiveTo determine the relationship between the dimensions of the distal femoral intercondylar notch (ICN) and the composition and metabolism of the anterior cruciate ligament (ACL) in three dog breeds with different relevant risks to ligament rupture and subsequent osteoarthritis (OA).DesignICN measurements were obtained from the femurs of Golden Retrievers (high risk), Labrador Retrievers (high risk) and Greyhounds (low risk). Femoral condyle width and height, ICN height and width indices, and notch shape index were measured using Vernier callipers in all dogs. Intact ACLs were obtained from the same dog breeds for a study of the impinged areas and were analysed for collagen content, collagen cross-links, and sulphated glycosaminoglycan (GAG) content, matrix metalloproteinase (MMP)-2 and the tissue inhibitors of metalloproteinases (TIMPs)-1 and -2.ResultsFemoral condyle width and height and ICN width indices were significantly greater in the low risk compared to the high risk breeds (P<0.01 for all parameters). In contrast, the pro (P=0.003) and active (P=0.007) forms of MMP-2 and sulphated GAGs (P=0.0002) were significantly greater in the impinged areas of the ACLs of the rupture predisposed breeds.ConclusionsImpingement by the ICN on the ACLs of the high risk breeds may result in increased collagen remodelling and increased sulphated GAG deposition, causing reduced structural integrity of the ligament. Altered ACL composition may predispose the ligament to increased laxity leading to joint degeneration and OA. This may have a comparative implication for pathogenesis of ACL rupture in humans

Epithelial cells respond to proteolytic and non-proteolytic detachment by enhancing interleukin-6 responses

Intestinal inflammatory disease or infection often results in the loss of the epithelial layer as a result mainly of the action of proteases, including the leucocyte serine proteinases (neutrophil elastase), lysosomal cathepsins and the matrix metalloproteinases from recruited inflammatory cells. Previous studies have shown that bronchial or intestinal epithelial cells (IEC) can respond to proteolytic attack by producing cytokines. In this study, we have determined the effect of protease treatment on interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) production by IEC lines. Both neutrophil elastase and trypsin treatment induced elevated levels of mRNA for IL-6 in rat IEC-6 cells. Non-proteolytic detachment of the IEC-6 cells also induced elevated levels of IL-6 mRNA, suggesting that the effect was not caused by a specific protease or degradation product, but probably by an effect on cell shape or cell detachment. Similar results were seen with the IEC-18 cell line. Trypsin treatment of the IEC-6 cells also enhanced unstimulated and IL-1β costimulated IL-6 secretion, but not MCP-1 secretion or mRNA levels. Finally, nuclear levels of the CCAAT/enhancer binding protein-β (C/EBP-β) were rapidly enhanced after proteolytic detachment of the IEC-6 cells, suggesting a mechanism for the enhancement of IL-6 mRNA responses. These data indicate that epithelial cells can respond to proteolytic attack or cell detachment by producing IL-6, a cytokine with several anti-inflammatory and antiprotease effects, which may be important in moderating the loss of the epithelial layer by its effects on nearby epithelial or inflammatory cells