Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis
| Autor: | William A. Blessing, Angie N. Sabogal, M. Belen Cubria, Lay-Hong Ang, Sebastian Suarez, Stephen Okajima, Edward K. Rodriguez, Patrick M. Williamson, Suzanne White, Ara Nazarian, Juan C. Villa-Camacho, Miguel Perez-Viloria, Evelyn Flynn, Mark W. Grinstaff |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
musculoskeletal diseases medicine.medical_specialty Population Urology Cell Line Injections Intra-Articular Rats Sprague-Dawley Mice Bursitis Fibrosis medicine Animals Humans Range of Motion Articular education Arthrofibrosis education.field_of_study Multidisciplinary Shoulder Joint business.industry Relaxin Frozen shoulder medicine.disease Rats Disease Models Animal Capsulitis PNAS Plus Female Collagen Contracture medicine.symptom business Range of motion Type I collagen |
| Zdroj: | Proceedings of the National Academy of Sciences. 116:12183-12192 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Arthrofibrosis is a prevalent condition affecting greater than 5% of the general population and leads to a painful decrease in joint range of motion (ROM) and loss of independence due to pathologic accumulation of periarticular scar tissue. Current treatment options are limited in effectiveness and do not address the underlying cause of the condition: accumulation of fibrotic collagenous tissue. Herein, the naturally occurring peptide hormone relaxin-2 is administered for the treatment of adhesive capsulitis (frozen shoulder) and to restore glenohumeral ROM in shoulder arthrofibrosis. Recombinant human relaxin-2 down-regulates type I collagen and α smooth muscle actin production and increases intracellular cAMP concentration in human fibroblast-like synoviocytes, consistent with a mechanism of extracellular matrix degradation and remodeling. Pharmacokinetic profiling of a bolus administration into the glenohumeral joint space reveals the brief systemic and intraarticular (IA) half-lives of relaxin-2: 0.96 h and 0.62 h, respectively. Furthermore, using an established, immobilization murine model of shoulder arthrofibrosis, multiple IA injections of human relaxin-2 significantly improve ROM, returning it to baseline measurements collected before limb immobilization. This is in contrast to single IA (sIA) or multiple i.v. (mIV) injections of relaxin-2 with which the ROM remains constrained. The histological hallmarks of contracture (e.g., fibrotic adhesions and reduced joint space) are absent in the animals treated with multiple IA injections of relaxin-2 compared with the untreated control and the sIA- and mIV-treated animals. As these findings show, local delivery of relaxin-2 is an innovative treatment of shoulder arthrofibrosis. |
| Databáze: | OpenAIRE |
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