Higher relaxin levels increases risk of anterior cruciate ligament injury
Relaxin is a hormone structurally related to insulin and insulin-like growth factor exerts its regulatory effect on the musculoskeletal and other systems through binding to its receptor in various tissues which is mediated by different signaling pathways. Relaxin changes the properties of cartilage and tendon by activating collagenase. This hormone is also involved in bone remodeling and healing of injured ligaments and skeletal muscle. It is found that high rate of ACL injuries has become a near epidemic problem to players, teams and the sports medicine community.
The peptide hormone relaxin found in female collegiate athletes has been shown to have collagenolytic effects on ligamentous tissue and revealed that anterior cruciate ligament injuries occur four times more often in women than in men as the concentrations of serum relaxin is above 6.0 pg/mL. However, relaxin receptors have recently been identified on human female anterior cruciate ligament (ACL), which result in an increase in matrix metalloproteinase (MMP) and decrease in tissue inhibitor of metalloproteinase (TIMP) gene expression, a decrease in collagen and alpha smooth muscle actin (αSMA) expression, inhibition of transforming growth factor β1 (TGFβ1)-induced fibrosis and an increase in cyclic adenosine 3',5'-monophosphate (cAMP) production and that these changes not seen in male ACL cells.
Ligament cells from ACL tissue were obtained from patients (7 male and 7 female) which were expanded in vitro. Patients were divided into certain groups and were administered with escalating concentrations of relaxin-2 as well as with TGFβ1 or 17β-estradiol. Further, with the aid of quantitative real-time polymerase chain reaction, these cells were lysed and analyzed for MMP1 (collagenase-1), MMP3 (stromelysin-1), MMP13 (collagenase-3), TIMP1, type I collagen, type III collagen, and/or αSMA mRNA expression and intracellular cAMP levels were assessed via an enzyme-linked immunoassay. However, relaxin exhibited no significant effect on male-derived ACL cell.
Results depicted that ACL injuries are more common in women than in men who participate in certain sports. Relaxin-2 significantly upregulated intracellular processes in human female ACL cells, but no effect was observed in male cells. Female athletes with higher circulating relaxin levels may be at risk of ACL injury.