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Bone Res. 2019 Mar 26;7:9. doi: 10.1038/s41413-019-0047-x. eCollection 2019.

Pathological mechanisms and therapeutic outlooks for arthrofibrosis.

Author information

1
1School of Biomedical Sciences, University of Western Australia, Crawley, Western Australia Australia.
2
2Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang China.
3
3School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia Australia.
4
4Hospital for Special Surgery, New York, NY USA.
5
5Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi China.
6
6Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi China.

Abstract

Arthrofibrosis is a fibrotic joint disorder that begins with an inflammatory reaction to insults such as injury, surgery and infection. Excessive extracellular matrix and adhesions contract pouches, bursae and tendons, cause pain and prevent a normal range of joint motion, with devastating consequences for patient quality of life. Arthrofibrosis affects people of all ages, with published rates varying. The risk factors and best management strategies are largely unknown due to a poor understanding of the pathology and lack of diagnostic biomarkers. However, current research into the pathogenesis of fibrosis in organs now informs the understanding of arthrofibrosis. The process begins when stress signals stimulate immune cells. The resulting cascade of cytokines and mediators drives fibroblasts to differentiate into myofibroblasts, which secrete fibrillar collagens and transforming growth factor-β (TGF-β). Positive feedback networks then dysregulate processes that normally terminate healing processes. We propose two subtypes of arthrofibrosis occur: active arthrofibrosis and residual arthrofibrosis. In the latter the fibrogenic processes have resolved but the joint remains stiff. The best therapeutic approach for each subtype may differ significantly. Treatment typically involves surgery, however, a pharmacological approach to correct dysregulated cell signalling could be more effective. Recent research shows that myofibroblasts are capable of reversing differentiation, and understanding the mechanisms of pathogenesis and resolution will be essential for the development of cell-based treatments. Therapies with significant promise are currently available, with more in development, including those that inhibit TGF-β signalling and epigenetic modifications. This review focuses on pathogenesis of sterile arthrofibrosis and therapeutic treatments.

Conflict of interest statement

The authors declare no competing interests.

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