Pathological mechanisms and therapeutic outlooks for arthrofibrosis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-12

AUTHORS

Kayley M. Usher, Sipin Zhu, Georgios Mavropalias, John A. Carrino, Jinmin Zhao, Jiake Xu

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. More... »

PAGES

9

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    http://scigraph.springernature.com/pub.10.1038/s41413-019-0047-x

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    http://dx.doi.org/10.1038/s41413-019-0047-x

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30937213


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