Dunkman Andrew A, Buckley Mark R, Mienaltowski Michael J, Adams Sheila M, Thomas Stephen J, Kumar Akash, Beason David P, Iozzo Renato V, Birk David E, Soslowsky Louis J
The McKay Orthopaedic Research Laboratory, University of Pennsylvania, 424 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104, USA.
Department of Molecular Pharmacology & Physiology, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd, MDC 8, Tampa, FL 33612, USA.
Matrix Biol. 2014 Apr;35:232-8. doi: 10.1016/j.matbio.2013.10.008. Epub 2013 Oct 21.
Recent studies have demonstrated that the small leucine-rich proteoglycans (SLRPs) biglycan and decorin impact tendon development, aging and healing in mature mice. However, despite the increased risk of tendon injury in the elderly, the role of SLRPs in tendon repair has not been investigated in aged animals. Therefore, our objective was to elucidate the influences of bigylcan and decorin on tendon healing in aged mice to relate our findings to previous work in mature mice. Since the processes of aging and healing are known to interact, our hypothesis was that aging mediates the role of biglycan and decorin on tendon healing. Patellar tendons from wild-type, biglycan-null and decorin-null mice were injured at 270 days using an established model. At 3 and 6 weeks post-surgery, structural, mechanical and biochemical analyses were performed and compared to uninjured controls. Early stage healing was inferior in biglycan-null and decorin-null mice as compared to wild type. However, tendons of all genotypes failed to exhibit improved mechanical properties between 3 and 6 weeks post-injury. In contrast, in a previous investigation of tendon healing in mature (i.e., 120 day-old) mice, only biglycan-null mice were deficient in early stage healing while decorin-null mice were deficient in late-stage healing. These results confirm that the impact of SLRPs on tendon healing is mediated by age and could inform future age-specific therapies for enhancing tendon healing.
最近的研究表明，富含亮氨酸的小分子蛋白聚糖（SLRPs）双糖链蛋白聚糖和核心蛋白聚糖会影响成熟小鼠的肌腱发育、老化和愈合。然而，尽管老年人肌腱损伤的风险增加，但SLRPs在老年动物肌腱修复中的作用尚未得到研究。因此，我们的目标是阐明双糖链蛋白聚糖和核心蛋白聚糖对老年小鼠肌腱愈合的影响，以便将我们的研究结果与之前在成熟小鼠中的研究工作联系起来。由于已知衰老和愈合过程会相互作用，我们的假设是衰老介导了双糖链蛋白聚糖和核心蛋白聚糖对肌腱愈合的作用。使用既定模型在270天时对野生型、双糖链蛋白聚糖基因敲除和核心蛋白聚糖基因敲除小鼠的髌腱进行损伤。在术后3周和6周，进行结构、力学和生化分析，并与未受伤的对照组进行比较。与野生型相比，双糖链蛋白聚糖基因敲除和核心蛋白聚糖基因敲除小鼠的早期愈合较差。然而，所有基因型的肌腱在损伤后3至6周均未表现出力学性能的改善。相比之下，在之前对成熟（即120日龄）小鼠肌腱愈合的研究中，只有双糖链蛋白聚糖基因敲除小鼠在早期愈合方面存在缺陷，而核心蛋白聚糖基因敲除小鼠在后期愈合方面存在缺陷。这些结果证实，SLRPs对肌腱愈合的影响是由年龄介导的，这可能为未来增强肌腱愈合的特定年龄疗法提供依据。
