Skeletal muscle injury--molecular changes in the collagen during healing

Changes in the collagen types and cross-linking of granulation and scar tissue in the injured site of partially ruptured gastrocnemius muscle were studied after a reproducible contusion injury to the left calf of a rat. In normal i.m. collagen the proportion of Type I collagen was considerably higher than Type III. Following injury there was a rapid increase in the proportion of Type III collagen reaching a maximum at 5 days after injury. After a further 2 days the proportion of Type I had increased significantly resulting in a decrease of the Type III/I ratio to below that of the control. However, as healing progressed there was a gradual shift back to the Type III/I ratio for normal i.m. collagen. The collagen produced in response to an injury was initially stabilized by the stable keto-imine cross-link hydroxylysino-5-keto-norleucine, characteristic of embryonic collagenous tissues. The proportion of the stable keto-imine cross-link gradually decreased, and a reversion to the cross-link pattern of normal uninjured i.m. collagenous connective tissue occurred towards the end of the 42-day follow-up period. The present biochemical study demonstrates that during the early phases of the repair process there is a reversion to the collagens typically present in high proportions in embryonic dermal connective tissue. This suggests that the fibroblasts have the ability to modify their product expression under varying circumstances. The study also demonstrates the importance of collagen cross-linking in determining the tensile strength of collagen fibre during the repair process.