Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Findings reported in The American Journal of Pathology suggest specialized proresolving mediators may become therapeutics that alleviate chronic tendon inflammation

Image shows interleukin IL-1beta stimulated tendon cells isolated from a patient with a shoulder tendon tear incubated in media containing either vehicle, 10nM Lipoxin B4 (LXB4), or 10nM Resolvin E1 (RvE1). Tendon cells were stained for inflammatory molecules pSTAT-1 (green) or IL-6 (red). LXB4 or RvE1 treatments moderate the pro-inflammatory phenotype of tendon cells, reducing expression of pSTAT-1 and IL6.

Philadelphia, October 10, 2019 - Tendon tears, both to the rotator cuff and Achilles heel, are common injuries, especially in aged individuals. Painful and disabling, they can adversely impact quality of life. New approaches are required to help patients suffering from chronic tendon injuries. A novel study in The American Journal of Pathology, published by Elsevier, identified mediators that promote resolution of inflammation as potential new therapeutics to push chronically injured tendons down an inflammation-resolving pathway.

"Our study informs new therapeutic approaches that target diseased cells and promote resolution of tendon inflammation, harnessing the body's own natural responses for therapeutic gain," explained Stephanie G. Dakin, PhD, BVetMed, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.

The study demonstrates the anti-inflammatory effects of two specialized proresolving mediators (SPMs), lipoxin B4 (LXB4) and Resolvin E1 (RvE1), on cultured tendon cells in which induced shoulder tendon disease was present.

According to Dr. Dakin and colleagues, resident (meaning part of the normal tissue) stromal cells, especially fibroblasts, play a pivotal role in inflammatory diseases of joints. After injury, fibroblasts become activated and show inflammation "memory," an important event underlying the switch from acute to chronic inflammation. These cells become unable to return to their normal state. The SPMs identified by the researchers interfere with this chronic inflammatory process and help fibroblasts resolve tendon inflammation; hence the name "proresolving" mediators.

Commenting on the study, Undurti N Das, MD, DSc, UND Life Sciences, Battle Ground, WA, USA, and BioScience Research Centre and Department of Medicine, GVP Medical College and Hospital, Visakhapatnam, India, emphasized that understanding the crosstalk among resident stromal cells including fibroblasts that not only participate in inflammatory diseases of the joint, but also in the switch from acute to chronic inflammation, tissue resident and infiltrating macrophages, infiltrating immune cells, and endothelial cells is important to the disease process and for the development of newer therapeutic interventions. 

"In this context, the report by Dakin et al is of substantial interest to the field. It establishes that tendon stromal cells isolated from patients with tendon tears show pro-inflammatory phenotype and secrete significantly higher amounts of interleukin (IL)-6 with dysregulated production and action of lipoxin A4, resolvins, protectins, and maresins compared to normal cells," added Dr. Das. 

"There is a clear unmet clinical need to develop effective new therapeutic approaches to treat tendon disease," added Dr. Dakin. "SPMs, including LXB4 and RvE1, may target diseased cells and potentiate resolution of chronic tendon inflammation."

Shoulder pain is the third most common cause of musculoskeletal pain, and tears affecting shoulder rotator cuff tendons comprise a large proportion of this disease burden. Current treatments for tendon injuries include physical therapy, non-steroidal anti-inflammatory drugs, platelet rich plasma, steroid injections, and surgery to repair torn tendons. These therapies are frequently ineffective, steroids are potentially harmful, and tendon tear surgery is associated with high postoperative failure rates. Therefore, alternative therapies targeting the cells driving chronic inflammation are required to help patients, and ideally avoid some of the problems associated with surgery, steroids, NSAIDS, or other interventions.

Similar stories

Clinical trial finds Azithromycin has no benefit against COVID-19

Main OCTRU

A clinical trial by University of Oxford researchers has confirmed that the antibiotic azithromycin has no clinical benefit in people with moderate COVID-19.

Study reveals the three most important aspects of care for hip fractures

Hip Main OCTRU Research Trauma

Older patients with hip fractures recover better if they receive treatment under the supervision of both a surgeon and a specialist in elderly care; are checked to avoid future falls; and are assessed for memory problems.

Major ERC funding awarded to Professor Michael Dustin

Awards Kennedy Main

Professor Michael Dustin and an international team of collaborators have been awarded a €10M grant from the European Research Council (ERC) to develop a new biotechnology around supramolecular attack particles (SMAPs) engineered to kill cancer cells.

The role of mAbs (neutralising monoclonal antibodies) in the fight against COVID-19

Main Research

Neutralising mAbs, a form of anti-viral medicine, are being explored as an attractive option to treat symptoms of COVID-19 and in some cases prevent infection. But what are the pros and cons of this type of treatment and what should regulators consider before granting approval?

Professor Michael Dustin elected to the National Academy of Sciences

Awards Kennedy Main

Recognised for his outstanding contributions to the field of immunology, Michael becomes the fourth Kennedy professor to be elected to the Academy.

Small mechanical forces in immune cells measured at unprecedented sensitivity

Kennedy Main Research

Oxford researchers have used advanced microscopy techniques to measure previously unseen forces generated by cells during an immune response; a breakthrough for mechanobiology and future advances in health and disease.