Time-dependent increases in type-III collagen gene expression in medial collateral ligament fibroblasts under cyclic strains

Numerous studies have demonstrated the capacity of mechanical strains to mo dulate cell behavior through several different signaling pathways. Understa nding the response of ligament fibroblasts to mechanically induced strains may provide useful knowledge for treating ligament injury and improving reh abilitation regimens. Biomechanical studies that quantify strains in the an terior cruciate and medial collateral ligaments have shown that these ligam ents are subjected to 4-5% strains during normal activities and can be stra ined to 7.7% during external application of loads to the knee joint. The ob jective of this study was to characterize the expression of types I and III collagen in fibroblast monolayers of anterior cruciate and medial collater al ligaments subjected to equibiaxial strains on flexible growth surfaces ( 0.05 and 0.075 strains) by quantifying levels of mRNA encoding these two pr oteins. Both cyclic strain magnitudes were studied under a frequency of 1 H z. The results indicated marked differences in responses to strain regimens not only between types I and III collagen mRNA expression within each cell type but also in patterns of expression between anterior cruciate and medi al collateral ligament cells. Whereas anterior cruciate ligament fibroblast s responded to cyclic strains by expression of higher levels of type-I coll agen message with almost no significant increases in type-III collagen, med ial collateral ligament fibroblasts exhibited statistically significant inc reases in type-III collagen mRNA at all time points after initiation of str ain with almost no significant increases in type-I collagen. Furthermore, d ifferences in responses by fibroblasts from the two ligaments were detected between the two strain magnitudes. In particular, 0.075 strains induced a time-dependent increase in type-III collagen mRNA levels in medial collater al ligament fibroblasts whereas 0.05 strains did not. The strain-induced ch anges in gene expression of these two collagens may have implications for t he healing processes in ligament tissue. The differences may explain, in pa rt, the healing differential between the anterior cruciate and medial colla teral ligaments in vivo.