Abstract
It is not known how extensively a localised flexor tendon injury affects the entire tendon. This study examined the extent of and relationship between histopathologic and gene expression changes in equine superficial digital flexor tendon after a surgical injury. One forelimb tendon was hemi-transected in six horses, and in three other horses, one tendon underwent a sham operation. After euthanasia at six weeks, transected and control (sham and non-operated contralateral) tendons were regionally sampled (medial and lateral halves each divided into six 3cm regions) for histologic (scoring and immunohistochemistry) and gene expression (real time PCR) analysis of extracellular matrix changes. The histopathology score was significantly higher in transected tendons compared to control tendons in all regions except for the most distal (P ≤ 0.03) with no differences between overstressed (medial) and stress-deprived (lateral) tendon halves. Proteoglycan scores were increased by transection in all but the most proximal region (P < 0.02), with increased immunostaining for aggrecan, biglycan and versican. After correcting for location within the tendon, gene expression for aggrecan, versican, biglycan, lumican, collagen types I, II and III, MMP14 and TIMP1 was increased in transected tendons compared with control tendons (P < 0.02) and decreased for ADAMTS4, MMP3 and TIMP3 (P < 0.001). Aggrecan, biglycan, fibromodulin, and collagen types I and III expression positively correlated with all histopathology scores (P < 0.001), whereas lumican, ADAMTS4 and MMP14 expression positively correlated only with collagen fiber malalignment (P < 0.001). In summary, histologic and associated gene expression changes were significant and widespread six weeks after injury to the equine SDFT, suggesting rapid and active development of tendinopathy throughout the entire length of the tendon. These extensive changes distant to the focal injury may contribute to poor functional outcomes and re-injury in clinical cases. Our data suggest that successful treatments of focal injuries will need to address pathology in the entire tendon, and that better methods to monitor the development and resolution of tendinopathy are required.
Highlights
Tendon injuries represent a major problem for the both the professional and leisure sporting communities[1,2]
There was palpable swelling associated with the surgical site in the horses with the partially transacted superficial digital flexor tendon (SDFT) that extended approximately 3cm proximal and distal to the surgical incision
The equine SDFT provides a novel model to investigate the mechanisms of tendinopathy, its length allowing detailed regional analysis not readily available in other species[31,32,33,34]
Summary
Tendon injuries represent a major problem for the both the professional and leisure sporting communities[1,2]. Either within the tendon itself or at the bone-tendon junction, is slow and the resulting tissue is often fibrotic without recapitulating normal structure, even after a prolonged rehabilitation. Pre-existing histopathologic tissue is highly prevalent in tendons of patients sustaining a spontaneous rupture[15] and ruptured Achilles tendons have a more degenerate histopathology than chronic pathological tendons[16]. This suggests that pre-existing degeneration is a predisposing factor to injury, and that following a tear further degenerative change occurs. How far from the injury such pathology extends is unclear
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