Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis.

Autor:	Blessing WA; Department of Biomedical Engineering, Boston University, Boston, MA 02215.; Department of Chemistry, Boston University, Boston, MA 02215.; Department of Medicine, Boston University, Boston, MA 02215., Okajima SM; Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Cubria MB; Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Villa-Camacho JC; Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Perez-Viloria M; Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Williamson PM; Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Sabogal AN; Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Suarez S; Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Ang LH; Confocal Imaging and IHC Core, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., White S; Confocal Imaging and IHC Core, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Flynn E; Orthopedic Research Laboratories, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115., Rodriguez EK; Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; ekrodrig@bidmc.harvard.edu mgrin@bu.edu anazaria@bidmc.harvard.edu., Grinstaff MW; Department of Biomedical Engineering, Boston University, Boston, MA 02215; ekrodrig@bidmc.harvard.edu mgrin@bu.edu anazaria@bidmc.harvard.edu.; Department of Chemistry, Boston University, Boston, MA 02215.; Department of Medicine, Boston University, Boston, MA 02215., Nazarian A; Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; ekrodrig@bidmc.harvard.edu mgrin@bu.edu anazaria@bidmc.harvard.edu.; Department of Orthopaedic Surgery, Yerevan State Medical University, Yerevan 0025, Armenia.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Jun 18; Vol. 116 (25), pp. 12183-12192. Date of Electronic Publication: 2019 Jun 03.
DOI:	10.1073/pnas.1900355116
Abstrakt:	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. Competing Interests: Conflict of interest statement: M.W.G., E.K.R., and A.N. are coinventors on a patent application submitted to the United States Patent and Trademark Office on the application of human relxin-2 as a treatment for arthrofibrosis.
Databáze:	MEDLINE
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