Cell phenotypic variation in normal and damaged tendons

Abstract

Injuries to tendons are common in both human athletes as well as in animals, such as the horse, which are used for competitive purposes. Furthermore, such injuries are also increasing in prevalence in the ageing, sedentary population. Tendon diseases often respond poorly to treatment and require lengthy periods of rehabilitation. The tendon has a unique extracellular matrix, which has developed to withstand the mechanical demands of such tensile-load bearing structures. Following injury, any repair process is inadequate and results in tissue that is distinct from original tendon tissue. There is growing evidence for the key role of the tendon cell (tenocyte) in both the normal physiological homeostasis and regulation of the tendon matrix and the pathological derangements that occur in disease. In particular, the tenocyte is considered to have a major role in effecting the subclinical matrix degeneration that is thought to occur prior to clinical disease, as well as in the severe degradative events that occur in the tendon at the onset of clinical disease. Furthermore, the tenocyte is likely to have a central role in the production of the biologically inadequate fibrocartilaginous repair tissue that develops subsequent to tendinopathy. Understanding the biology of the tenocyte is central to the development of appropriate interventions and drug therapies that will either prevent the onset of disease, or lead to more rapid and appropriate repair of injured tendon. Central to this is a full understanding of the proteolytic response in the tendon in disease by such enzymes as metalloproteinases, as well as the control of the inappropriate fibrocartilaginous differentiation. Finally, it is important that we understand the role of both intrinsic and extrinsic cellular elements in the repair process in the tendon subsequent to injury.

Figure 1

(a) Longitudinal haemotoxylin and eosin stained section of a normal mid metacarpal (tensional) region of a superficial digital flexor tendon from an 8-year-old thoroughbred racehorse. Note the flattened nuclei of the tenocytes which lie between the parallel aligned collagen fibrils. The more cellular region is the endotenon which lies between tendon fascicles. (b) Longitudinal haemotoxylin and eosin stained section of a mid metacarpal (tensional) region of a superficial digital flexor tendon from an 8-year-old thoroughbred racehorse which sustained a tendon injury approximately 8 weeks previously. There appears to be a disorganized arrangement to the cells in the injured site and a loss of parallel alignment. The cells appear to be morphologically heterogeneous compared to the cellular element seen in normal tendon, with a distinct loss of cells with flattened nuclei at the site of pathology.

Figure 2

Transverse ultrasound scan of the mid-metacarpal region of the left and right superficial digital flexor tendon (SDFT) from an 9-year-old thoroughbred racehorse which sustained a tendon injury approximately 2 weeks previously. The SDFTs are identified by the white arrows. There is a loss of echogenicity in the central region of the tendons which is due to rupture of tendon fibres at that site (yellow arrow). The injury is more apparent on the left in comparison with the right limb. [Please refer to the electronic article for the colour version of this figure (http://www.blackwell-synergy.com/loi/iep)].

Figure 3

Transverse ulatrsonogram of the mid-metacarpal region of the left superficial digital flexor tendon (SDFT) and deep digital flexor tendon (DDFT) from an 6-year-old thoroughbred racehorse which sustained a tendon injury 10 days previously. There is an anechoic and hypoechoic region in the tendon as a result of a tendon injury at that site (white arrow). [Please refer to the electronic article for the colour version of this figure (http://www.blackwell-synergy.com/loi/iep)].