Arthrofibrosis is the accumulation of fibrotic, collagenous tissue within the joint space that occurs after a trauma, surgery, or idiopathically. It manifests as a painful decrease in joint range of motion, limiting even quotidian and basic activities of life for prolonged periods of a year or more, depending on severity and joint location. In the US alone, there are approximately three million patients each year who undergo trauma and/or surgery in joints susceptible to arthrofibrosis including the shoulder, knee, and elbow as well as another nine million who currently suffer from shoulder arthrofibrosis. Herein, we demonstrate the potential of using a naturally occurring, antifibrotic hormone, relaxin-2, to combat the arthrofibrotic phenotype. Its promise as a therapeutic for arthrofibrosis stems from its biological role in preparing the pubic symphysis for child birth during the late stages of pregnancy by promoting the expression of matrix metalloproteases and suppressing the expression of tissue inhibitors of matrix metalloproteases and fibrous proteins. In this work, we use relaxin in three different treatment groups to test its efficacy in restoring full function and range of motion in an established murine model of shoulder contracture: multiple intravenous injections, a single intra-articular injection, and multiple intra-articular injections. After inducing trauma to the shoulder of Sprague-Dawley rats, multiple intravenous injections and single intra-articular injections showed minimal effects in improving the arduous recovery process for shoulder contractions. Multiple intra-articular injections of relaxin-2, however, not only restored range of motion of the shoulder to baseline level, but also decreased excess deposition of fibrotic proteins in the synovial space without any toxic side effects. These findings were corroborated biomechanically and histologically. We also reveal its promise for translation to a clinically-relevant therapy by showing that relaxin-2 downregulates type I collagen deposition in primary human synoviocytes. Local and continuous administration of relaxin-2 into the synovial space therefore presents itself as a candidate therapeutic for reversing arthrofibrosis.         <br/>

Intra-articular injection of relaxin-2 alleviates shoulder arthrofibrosis

256th National Meeting (2018)

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