No abstract

Using a rabbit model of flexor tendon injury, mRNA levels for a subset of relevant molecules involved in inflammatory and fibrotic processes were assessed by reverse transcriptase-polymerase chain reaction 3, 6, 12 and 24 days after injury. Increased levels of COX-2, IL-1beta, MMP-13 and TIMP-1 mRNA were detected in both tendon and tendon sheath following injury, with each molecule exhibiting tissue and time-dependent changes. MMP-13 and TIMP-1 mRNA levels were markedly upregulated in both tissues, whereas COX-2 and IL-1beta predominantly increased in tendon. Both hyaluronan synthase (HAS) 2 and 3 exhibited increases in mRNA levels in tendon tissue after injury, HAS 2 being more pronounced. These findings support the concept that healing in the flexor tendon and the sheath involve different molecular events and that each tissue may require unique modifications if healing is to be enhanced and adhesions reduced.

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

This study analysed the differences on a molecular level between two segments of the deep flexor tendon, and compared the intrasynovial flexor tendon with the tendon sheath and the extrasynovial peroneus tendon in a rabbit model. The TRIspin method of RNA extraction was combined with the reverse transcription polymerase chain reaction to assess mRNA levels in the tissue segments. Significant differences were detected for all genes studied. mRNA levels for aggrecan, biglycan and collagen III were significantly higher in the fibrocartilaginous proximal segment of the flexor tendon. Collagen I was higher in the flexor tendon than the sheath and the peroneus tendon, and TGF-beta1 was significantly lower in the peroneus tendon. This study demonstrates differences at the mRNA level between different segments of tendon, indicating that the tendon tissue may be adapted to its environment.