Patterns of mRNA expression for matrix molecules and growth factors in flexor tendon injury: Differences in the regulation between tendon and tendon sheath

Purpose: Injuries to tendons, particularly flexor tendons, can lead to loss of function after healing due to adhesion formation and other complications. The aim of this study was to increase our understanding of the healing process in tendons and tendon sheaths to develop methods to affect the healing process and improve the outcome of tendon repair in the future. Methods: In a rabbit model of flexor tendon injury, tissues were harvested 3, 6, 12, and 24 days after surgery (n = 6 for each group). After RNA extraction, messenger RNA (mRNA) levels for relevant genes in tendon and tendon sheaths were measured using the reverse transcription polymerase chain reaction. Messenger RNA levels for a subset of relevant molecules at different time points after injury were compared with those of uninjured controls for tendons and tendon sheaths. Results: Initially after injury, there was a shift in collagen expression with a marked increase in type III mRNA levels in both the tendon and tendon sheath, whereas those for collagen I increased only in the sheath at later time points. Aggrecan and versican mRNA levels were increased in both tissues, but temporal aspects of the changes were-different. The mRNA levels for biglycan and lumican were all upregulated throughout the healing interval examined, whereas those for decorin were significantly decreased throughout in the tendon more so than the sheath. The mRNA levels for basic fibroblastic growth factor and transforming growth factor beta were elevated after injury in the tendon but not in the sheath. In contrast, mRNA levels for connective tissue growth factor were unaltered or decreased in both tissues throughout the interval assessed. Conclusions: Healing after injury to the rabbit flexor tendon and tendon sheath follow a reproducible pattern of gene expression; however, the pattern in the tendon is very different from that in the sheath. These findings indicate that interventions developed to improve healing of these tissues will have to address these differences, because they will likely affect the outcomes.