An Overview of the Basic Biology of Tendon and Ligament Disease

Tendon and ligament disease are significant clinical problems, most particularly in horses and dogs in the superficial digital flexor tendon (SDFT) and cranial cruciate ligament (CCL) respectively. This overview will firstly cover the hierarchical structure including fascicular subunits and the cellular populations. Fibroblasts in tendon/ igament, termed tenocytes and desmocytes respectively, have increasingly been a research focus as they are responsible for synthesis and turnover of all extracellular matrix components. Type 1 and 2 tenocytes have spindle-shaped and cigar-shaped nuclei and have been referred to as “tenocytes” and “tenoblasts” respectively. Type 3 cells have a chondrocyte-like appearance and tend to be found in areas experiencing compressive force, where there is a fibrocartilaginous matrix. The type 1 and 2 cells form networks linked by adherens and gap junctions, with cellular processes wrapping around the longitudinally arranged collagen fibrils. There is increasing evidence for the presence of tendon stem/progenitor cells (TSPCS); their exact site within the tissue is not known, with both intrafascicular and perivascular locations proposed.

Although some injuries occur due to violent and unusual direct or indirect mechanical force, many ruptures involve tendon/ligament tissue that has become weakened over an undefined period of time. This accumulation of (subclinical) microdamage is usually age- and exercise-related. Tenocytes do constantly repair damage; repair failure may occur because matrix breakdown is too frequent or severe, but there is increasing evidence that direct cellular damage or death, or stimulation of inappropriate cellular responses are at least contributory. This is referred to as the “tendonosis cycle”, where cellular death and/or dysfunction lead to further weakening of the matrix, and therefore a greater predisposition to insult. The role of TSPCs in repairing this microdamage is not known. It seems likely that there is a continuum of pathology in tendons/ligaments from cellular reaction through dysrepair, to degeneration, at which point reversibility is unlikely.  [...]