Serum relaxin is correlated with relaxin receptors and MMP-1 in the anterior oblique ligament

Purpose: Introduction: Relaxin is a hormone produced in pregnancy, mediated at the cellular level by damage to the extracellular matrix. We hypothesized that relaxin was a target hormone involved in the development of trapeziometacarpal (TM) joint laxity, potentially as a cause of ligament loosening and attrition, and later osteoarthritis. The purpose of this study was to quantitatively evaluate relaxin receptors in the anterior oblique ligament of the thumb as well as the relationship of serum relaxin and matrix metalloproteases (MMPs) to these receptors. Methods: Consecutive patients undergoing carpometacarpal joint arthroplasty with trapeziectomy and ligament reconstruction by two hand surgeons were enrolled prospectively. Patients underwent examination of laxity using the Beighton-Horan measurement, blood draw for serum relaxin, and sampling of the anterior oblique ligament during surgery. Serum relaxin was determined by enzyme-linked immunosorbent assay (ELISA). The ligament underwent extraction of RNA and analysis with quantitative reverse-transcriptase polymerase-chain reaction (qRT-PCR) for relaxin receptor (RXFP-1), MMP-1, and MMP-3. Results: A total of 49 patients were enrolled, including 30 women and 19 men with an average age of 62 (range, 43-78 years). Serum relaxin levels averaged 3.73 pg/ml (range, 0-9.45). The mean RXFP-1 receptor level was 5.23 x 106 attograms (ag), while MMP-1 and MMP-3 were expressed at much higher levels (0.022 ag and 0.318 ag, respectively). When compared to the serum relaxin levels in these patients, there was a significant relationship between serum relaxin and the log of RXFP-1 (p=0.02) and MMP-1 (p=0.05), using Pearson correlations and linear regression analysis. Conclusions: These findings confirm the presence of relaxin receptors in the anterior oblique ligament as well as MMPs 1 and 3, which are known to be upregulated by relaxin binding. The relationship between serum relaxin and RXFP-1 and MMP-1 suggests that as circulating relaxin levels rise, increased ligamentous attenuation could potentially occur in the anterior oblique ligament. This may be a factor in the development of trapeziometacarpal arthritis.