VEGF, VEGFR-1, and CTGF cell densities in tendon are increased-with cyclical loading: An in vivo tendinopathy model

Tendon injuries can occur in athletes and workers whose tasks involve repetitive, high-force hand activities, but the early pathophysiologic processes of tendinopathy are not well known. The purpose of this animal study was to evaluate the effects of cyclical tendon loading on the densities of cells producing growth factors such as vascular endothelial growth factor (VEGF), its receptor, vascular endothelial growth factor receptor 1 (VEGFR-1), and connective tissue growth factor (CTGF) in the Flexor Digitorum Profundus (FDP) tendon at the epicondyle. The FDP muscles of nine New Zealand rabbits were electrically stimulated to contract repetitively for 80 h of cumulative loading over 14 weeks. The contralateral limbs served as controls. The tendons at the medial epicondyle insertion sites were harvested, and sections were immunostained with antibodies directed against VEGF, VEGFR-1, or CTGF. Positive-staining cells were counted in six regions of interest: three along the enthesis, and three corresponding regions 1500 microns distal to the enthesis. VEGF (p = 0.0001), VEGFR-1 (p = 0.046), and CTGF (p = 0.0001) cell densities were increased in the tendon of the loaded limb compared to the nonloaded limb. In addition, regional differences in VEGF, VEGFR-1, and CTGF cell densities were found. VEGF, VEGFR-1, and CTGF are increased in tendon experiencing cyclical loading and may play a role in the early vascular changes in the progression to tendinosis