Department of Health and Kinesiology, Purdue University, West Lafayette, IN, United States.
Connect Tissue Res. 2023 Mar;64(2):161-174. doi: 10.1080/03008207.2022.2135508. Epub 2022 Oct 25.
Delayed tendon healing is a significant clinical challenge for those with diabetes. We explored the role of advanced glycation end-products (AGEs), a protein modification present at elevated levels in serum of individuals with diabetes, on injured and intact tendons using a mouse model. Cell proliferation following tissue injury is a vital component of healing. Based on our previous work demonstrating that AGEs limit cell proliferation, we proposed that AGEs are responsible for the delayed healing process commonly observed in diabetic patients. Further, in pursuit of interventional strategies, we suggested that moderate treadmill exercise may support a healing environment in the presence of AGEs as exercise has been shown to stimulate cell proliferation in tendon tissue.
Mice began receiving daily intraperitoneal injections of bovine serum albumin (BSA)-Control or AGE-BSA injections (200μg/ml) at 16-weeks of age. A tendon injury was created in the central third of both patellar tendons. Animals assigned to an exercise group began a moderate treadmill protocol one week following injury. The intact Achilles tendon and soleus muscle were also evaluated to assess the effect of BSA and AGE-BSA on un-injured muscle and tendon.
We demonstrate that our injection dosing and schedule lead to an increase in serum AGEs. Our findings imply that AGEs indeed modulate gene expression following a patellar tendon injury and have modest effects on gene expression in intact muscle and tendon.
While additional biomechanical analysis is warranted, these data suggest that elevated serum AGEs in persons with diabetes may impact tendon health.
糖尿病患者的肌腱愈合延迟是一个重大的临床挑战。我们使用小鼠模型探索了晚期糖基化终产物（AGEs）的作用，AGEs 是糖尿病患者血清中高水平存在的一种蛋白质修饰物，对受伤和未受伤的肌腱都有影响。组织损伤后的细胞增殖是愈合的重要组成部分。基于我们之前的工作表明 AGEs 限制细胞增殖，我们提出 AGEs 是导致糖尿病患者常见愈合延迟的原因。此外，为了寻找干预策略，我们建议适度的跑步机运动在存在 AGEs 的情况下可能支持愈合环境，因为运动已被证明可以刺激肌腱组织中的细胞增殖。
16 周龄时，小鼠开始每天接受牛血清白蛋白（BSA）-对照或 AGE-BSA（200μg/ml）的腹腔内注射。在髌腱的中央三分之一处造成肌腱损伤。分配到运动组的动物在受伤后一周开始进行适度的跑步机方案。还评估了完整的跟腱和比目鱼肌，以评估 BSA 和 AGE-BSA 对未受伤的肌肉和肌腱的影响。
我们证明我们的注射剂量和方案导致血清 AGEs 增加。我们的发现表明，AGEs 确实在髌腱损伤后调节基因表达，并且对未受伤的肌肉和肌腱的基因表达有适度的影响。
虽然需要进行更多的生物力学分析，但这些数据表明，糖尿病患者血清中升高的 AGEs 可能会影响肌腱健康。
