Advances in the understanding of tendinopathies: A report on the Second Havemeyer Workshop on equine tendon disease

Tendons are formed during the second half of embryonic developmentwhen tendon precursor cells deposit narrow-diameter (∼30 nm) collagenfibrils that are parallel to the long axis of the tissue. During post nataldevelopment, the narrow fibrils are replaced by large-diameter (up to500 nm)fibrils.Theabilityoftendontotransmitforcefrommuscletobone,and to dissipate forces during locomotion, is directly attributable to thecollagen fibrils. How the fibrils are synthesised, how they are alignedparallel to the tendon long axis, and how this arrangement can bereinstated during tendon healing are poorly understood. Ultrastructuralstudies of tendon lesions show the reappearance of narrow-diametercollagen fibrils and cells with slender cytoplasmic protrusions (calledfibripositors) that normally only occur in tendon during embryonicdevelopment. Recapitulation of development is a hypothesis that isgaining increasing support from researchers of tendon disease. A betterunderstanding of the genetic, molecular and environmental cues duringembryonicdevelopmentisexpectedtoprovidebetterinsightsintohowtoimprove the rate and fidelity of tendon repair in mature horses. Tendondevelopment can conveniently be considered to have an early ‘cellular’phaseandasubsequent‘matrix’phase.Inthematrix-dominatedphaseoftendon development 3D scanning electron microscopy of mouse tendonsuggests that fibripositors of the cells are the site of new fibril formationandthemechanicalinterfacebetweenthecellandtheextracellularmatrix.It is hypothesised that fibripositors exert pulling forces on collagen fibrils,and their cellular forces require functional myosin II, which is anintracellular molecular motor that is part of the actinomyosin system. Adetailed understanding of how cells set the tensional homeostasis oftendon is expected to lead to new strategies for regulating collagen fibrilassemblyinhealthandintendinopathy.