Intra-Articular Injection of Relaxin-2 Alleviates Arthrofibrosis in Mouse Model of Shoulder Arthrofibrosis

Arthrofibrosis is a condition affecting greater than 5% of the general population. Patients with arthrofibrosis experience a painful decrease in joint range of motion (ROM) and loss of functionality due to pathologic accumulation of periarticular scar tissue. Current treatment options (Physical therapy, joint manipulation, surgical release), are limited in effectiveness and do not address the accumulation of fibrotic collagenous tissue. We report the reversal of arthrofibrotic symptoms and pathology in a non-traumatic murine model of shoulder arthrofibrosis upon administration of human relaxin-2. After 8 weeks of forelimb immobilization, animals treated with relaxin-2 experience significantly greater range of motion and reduced fibrotic collagenous tissue in the glenohumeral joint compared to untreated control animals. Biomechanical and histological outcome measures are dependent on the relaxin-2 administration route. We tested multiple intravenous injections ; single intra-articular injection ; or multiple intra-articular injections . Only multiple local intra-articular injections of relaxin-2 restore joint ROM and return the joint to the healthy baseline state as demonstrated by histological analyses and motion assessment. Within this group, the histological hallmarks of contracture are also absent when compared to the untreated control animals. Human relaxin-2 also downregulates type I collagen production in human fibroblast-like synoviocytes. These findings support translation to humans and the local delivery of human relaxin-2 as a potential paradigm shift in the treatment of arthrofibrosis.