Growth factor and protease expression during different phases of healing after rabbit deep flexor tendon repair

Abstract

The purpose of the study was to contribute to the mapping of molecular events during flexor tendon healing, in particular the growth factors insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), matrix metalloproteinases (MMP-3 and MMP-13) and their inhibitors (tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-3, and the protease cathepsin K. In a rabbit model of flexor tendon injury, the mRNA expression for the growth factors, MMPs and TIMPs were measured in tendon and tendon sheath tissue at several time points (3, 6, 21, and 42 days) representing different phases of the healing process. We found that MMP-13 remained increased during the study period, whereas MMP-3 returned to normal levels within the first week after injury. TIMP-3 was down-regulated in the tendon sheaths. Cathepsin K was up-regulated in tendons and sheaths after injury. NGF was present in both tendons and sheaths, but unaltered. IGF-1 exhibited a late increase in the tendons, while VEGF was down-regulated at the later time points. In conclusion, we have demonstrated the presence of NGF in flexor tendons. MMP-13 expression appears to play a more protracted role in flexor tendon healing than MMP-3. The relatively low levels of endogenous IGF-1 and VEGF mRNA following injury support their potential beneficial role as exogenous modulators to optimize tendon healing and strength without increasing adhesion formation. ß

Impaired biomechanical properties correlate with neoangiogenesis as well as VEGF and MMP‐3 expression during rat patellar tendon healing

“…The influence of intrinsic VEGF expression during tendon healing on biomechanical properties of the degenerated tendon could be shown in the presented rat model. HIF-1/VEGF-induced angiogenesis not only supports tissue repair and remodeling of the injured tendon, 27 but also impairs its biomechanical stability by degradation of the extracellular matrix during endothelial invasion. 28 Secretion of MMPs facilitates capillary growth by matrix degradation.…”

The effect of diclofenac on matrix metalloproteinase levels in the rotator cuff

“…In a study that compared MMP levels during healing course of deep flexor tendon in rabbits, a 9-fold increase was observed in levels of MMP-3, and 30-fold increase in levels of MMP-13 after injury. While levels of MMP-13 remained high during the study period of 42 days, levels of MMP-3 returned to pre-injury levels at week 1 [14]. Based on these results, Berglund et al [14] indicated that MMP-3 is involved in early healing process while MMP-13 plays a role in remodeling.…”

“…While levels of MMP-13 remained high during the study period of 42 days, levels of MMP-3 returned to pre-injury levels at week 1 [14]. Based on these results, Berglund et al [14] indicated that MMP-3 is involved in early healing process while MMP-13 plays a role in remodeling. In the present study, levels of MMP-13 were similar in control groups who were not treated with the drug while they tended to gradually decrease in study groups towards the sixth week.…”

“…Some focused on the role of MMPs during phases of tendon healing [6,9,10,[14][15][16]. The present study contributes to the literature by evaluating the effect of diclofenac on the MMP levels during phases of tendon healing as well as on the biomechanical outcomes.…”

Growth Hormone Does Not Stimulate Early Healing in Rat Tendons

“…In contrast, several animal studies have demonstrated up-regulation of the IGF-1 expression during tendon healing [6,7,9]. This up-regulation was seen both during an early and a later phase of healing.…”