Biasutti Sara, Dart Andrew, Smith Margaret, Blaker Carina, Clarke Elizabeth, Jeffcott Leo, Little Christopher
Research and Clinical Training Unit, University Veterinary Teaching Hospital, University of Sydney, Camden, Australia.
Raymond Purves Bone and Joint Research Laboratory, The Kolling Institute, Sydney Medical School, The University of Sydney, Sydney, Australia.
PLoS One. 2017 Oct 12;12(10):e0185282. doi: 10.1371/journal.pone.0185282. eCollection 2017.
Flexor tendinopathy is a common problem affecting humans and animals. Tendon healing is poorly understood and the outcomes of conservative and surgical management are often suboptimal. While often considered a localized injury, recent evidence indicates that in the short term, tendinopathic changes are distributed widely throughout the tendon, remote from the lesion itself. Whether these changes persist throughout healing is unknown. The aim of this study was to document gene expression, histopathological and biomechanical changes that occur throughout the superficial digital flexor tendon (SDFT) up to 16 weeks post-injury, using an ovine surgical model of tendinopathy. Partial tendon transection was associated with decreased gene expression for aggrecan, decorin, fibromodulin, tissue inhibitors of metalloproteinases (TIMPS 1, 2 and 3), collagen I and collagen II. Gene expression for collagen III, lumican and matrix metalloproteinase 13 (MMP13) increased locally around the lesion site. Expression of collagen III and MMP13 decreased with time, but compared to controls, collagen III, MMP13 and lumican expression remained regionally high throughout the study. An increase in TIMP3 was observed over time. Histologically, operated tendons had higher pathology scores than controls, especially around the injured region. A chondroid phenotype was observed with increased cellular rounding and marked proteoglycan accumulation which only partially improved with time. Biomechanically, partial tendon transection resulted in a localized decrease in elastic modulus (in compression) but only at 8 weeks postoperatively. This study improves our understanding of tendon healing, demonstrating an early 'peak' in pathology characterized by altered gene expression and notable histopathological changes. Many of these pathological changes become more localized to the region of injury during healing. Collagen III and MMP13 expression levels remained high close to the lesion throughout the study and may reflect the production of tendon tissue with suboptimal biomechanical properties. Further studies evaluating the long-term response of tendon to injury (6-12 months) are warranted to provide additional information on tendon healing and provide further understanding of the mechanisms underlying the pathology observed in this study.
屈肌腱病是影响人类和动物的常见问题。肌腱愈合的机制尚不清楚，保守治疗和手术治疗的效果往往不尽人意。虽然通常被认为是局部损伤，但最近的证据表明，在短期内，肌腱病性改变广泛分布于整个肌腱，远离病变本身。这些变化在整个愈合过程中是否持续尚不清楚。本研究的目的是利用绵羊肌腱病手术模型，记录损伤后长达16周的指浅屈肌腱（SDFT）中发生的基因表达、组织病理学和生物力学变化。部分肌腱横断与聚集蛋白聚糖、核心蛋白聚糖、纤维调节素、金属蛋白酶组织抑制剂（TIMP 1、2和3）、胶原蛋白I和胶原蛋白II的基因表达降低有关。胶原蛋白III、光蛋白聚糖和基质金属蛋白酶13（MMP13）的基因表达在病变部位局部增加。胶原蛋白III和MMP13的表达随时间下降，但与对照组相比，在整个研究过程中，胶原蛋白III、MMP13和光蛋白聚糖的表达在局部区域仍保持较高水平。随着时间的推移，观察到TIMP3增加。组织学上，手术肌腱的病理评分高于对照组，尤其是在损伤区域周围。观察到软骨样表型，细胞变圆增加，蛋白聚糖明显积聚，且仅随时间部分改善。生物力学方面，部分肌腱横断导致弹性模量局部降低（在压缩时），但仅在术后8周出现。本研究增进了我们对肌腱愈合的理解，证明了以基因表达改变和显著组织病理学变化为特征的早期病理“峰值”。在愈合过程中，许多这些病理变化在损伤区域变得更加局限。在整个研究过程中，胶原蛋白III和MMP13的表达水平在病变附近仍保持较高，这可能反映了具有次优生物力学特性的肌腱组织的产生。有必要进一步研究评估肌腱对损伤的长期反应（6 - 12个月），以提供有关肌腱愈合的更多信息，并进一步了解本研究中观察到的病理机制。
