Washington University in St. Louis, St. Louis, Missouri.
University of the Ryukyus, Okinawa, Japan.
J Bone Joint Surg Am. 2021 May 5;103(9):e36. doi: 10.2106/JBJS.20.01253.
Environmental conditions strongly influence the healing capacity of connective tissues. Well-vascularized extrasynovial tendons typically undergo a robust wound-healing process following transection and repair. In contrast, avascular intrasynovial tendons do not mount an effective repair response. The current study tests the hypothesis that flexor tendons, as a function of their synovial environment, exhibit unique inflammatory, angiogenic, and metabolic responses to injury and repair.
Flexor tendons present a distinct opportunity to test the study hypothesis, as they have proximal regions that are extrasynovial and distal regions that are intrasynovial. In an internally controlled study design, the second and fifth forepaw flexor tendons were transected and repaired in either the extrasynovial or the intrasynovial anatomical region. Histological, gene expression, and proteomics analyses were performed at 3 and 7 days to define the early biological events that drive synovial environment-dependent healing responses.
Uninjured intrasynovial tendons were avascular, contained high levels of proteoglycans, and expressed inflammatory factors, complement proteins, and glycolytic enzymes. In contrast, extrasynovial tendons were well vascularized, contained low levels of proteoglycans, and were enriched in inflammation inhibitors and oxidative phosphorylation enzymes. The response to injury and repair was markedly different between the 2 tendon regions. Extrasynovial tendons displayed a robust and rapid neovascularization response, increased expression levels of complement proteins, and an acute shift in metabolism to glycolysis, whereas intrasynovial tendons showed minimal vascularity and muted inflammatory and metabolic responses.
The regional molecular profiles of intact and healing flexor tendons revealed extensive early differences in innate immune response, metabolism, vascularization, and expression of extracellular matrix as a function of the synovial environment. These differences reveal mechanisms through which extrasynovial tendons heal more effectively than do intrasynovial tendons.
To improve outcomes after operative repair, future treatment strategies should promote features of extrasynovial healing, such as enhanced vascularization and modulation of the complement system and/or glucose metabolism.
环境条件强烈影响结缔组织的愈合能力。富含血管的关节外肌腱在横断和修复后通常会经历强大的愈合过程。相比之下，无血管的关节内肌腱不会产生有效的修复反应。本研究检验了这样一个假设，即屈肌腱作为其滑膜环境的功能，表现出对损伤和修复的独特的炎症、血管生成和代谢反应。
屈肌腱提供了一个独特的机会来检验研究假设，因为它们的近端区域是关节外的，而远端区域是关节内的。在内部对照研究设计中，第二和第五前爪屈肌腱在关节外或关节内解剖区域横断和修复。在 3 天和 7 天进行组织学、基因表达和蛋白质组学分析，以确定驱动滑膜环境依赖性愈合反应的早期生物学事件。
未受伤的关节内肌腱是无血管的，含有高水平的蛋白聚糖，并表达炎症因子、补体蛋白和糖酵解酶。相比之下，关节外肌腱富含血管，含有低水平的蛋白聚糖，富含炎症抑制剂和氧化磷酸化酶。两种肌腱区域对损伤和修复的反应明显不同。关节外肌腱显示出强大而快速的血管生成反应，补体蛋白表达水平增加，以及代谢向糖酵解的急性转变，而关节内肌腱显示出最小的血管生成和减弱的炎症和代谢反应。
完整和愈合的屈肌腱的区域分子谱揭示了固有免疫反应、代谢、血管生成和细胞外基质表达的早期广泛差异，这取决于滑膜环境。这些差异揭示了关节外肌腱比关节内肌腱更有效地愈合的机制。
为了提高手术修复后的结果，未来的治疗策略应促进 extrasynovial 愈合的特征，如增强血管生成和补体系统和/或葡萄糖代谢的调节。
