Abstract
Rotator cuff tendon injuries are common, particularly amongst patients who suffer from type 2 diabetes mellitus and patients with a history of smoking. In these patients, rotator cuff injuries also heal more slowly and are more likely to recur. The cellular and molecular processes underlying the tendon healing process, at times inflammatory by nature, are well-known. However, where along that process diabetes and tobacco use exacerbate the problem has yet to be understood.|Advanced glycation end products (AGEs) may be the culprit. AGE accumulation is increased in both diabetic and tobacco-using groups, and AGEs are known to exacerbate the more inflammatory or critical stages of the cellular and molecular healing process. Collagen phenotype, expressed as the ratio of Collagen type 1 to Collagen type 3, is the primary determinant underlying tendon injury and impaired healing. This study was conducted to assess AGEs as a causal event in impaired tendon healing, particularly by way of increasing levels of matrix metalloproteinases, namely MMP2 and MMP9.|Human tendon tissue recovered as surgical waste was utilized to assess the correlation between these and other relevant molecules in the injured tendon. Following, swine tenocytes in cell culture were treated with cigarette smoke condensate, AGE inhibitor (pyridoxamine), and both in order to assess AGEs as a causal factor in terms of expression change in MMP2, MMP9, and the Pro-Collagen 1:3 ratio.|Cigarette smoke condensate containing tobacco-derived AGEs was found to increase MMP2 and decrease the Pro-Collagen 1:3 ratio, suggesting that increased AGE accumulation does underlie impaired healing processes in diabetic and smoking patients with rotator cuff injuries. Findings suggest that this is accomplished through MMP2-mediated suppression of Pro- Collagen 1:3 ratio.|The results of this work are encouraging and set the stage to uncover the pathways that interfere with tendon healing. Verification of our results by replication in a larger sample of patients’ tissues as well as considering in vivo studies is necessary to draw a strong conclusion. In addition, the results may show that Pyridoxamine, which functions to inhibit the production of AGEs, may not be protective against already-synthesized AGEs due to the history of tobacco smoking and diabetes. Nonetheless, further search should be done into developing a more clinically relevant AGE inhibitor.