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

NDORMS researchers awarded for Dupuytren research

Awards Hand Kennedy Main

Three NDORMS researchers have received awards from the International Dupuytren Society, a patient organisation that brings together Dupuytren Disease patient societies from across the world.

Hope for rheumatoid arthritis patients who are non-responsive to anti-TNF

Arthritis Kennedy Main

New research published in The Lancet shows that tocilizumab is a more effective treatment than rituximab for rheumatoid arthritis patients with a poor response to anti-tumour necrosis factor (TNF).

A new study maps the expression of innate immune receptors during the course of arthritis

Arthritis Kennedy Main

The research, which was a collaboration with researchers from Oxford University and Queen Mary University of London and published in Journal of Autoimmunity, looked at changes in receptors known as toll-like receptors (TLRs) in arthritis at different stages of disease.

International Women's Day

Department Main

It’s International Women's Day! This year’s theme is #Choosetochallenge. We’re celebrating some of the amazing women at NDORMS, and asking them what changes they’d like to see in medical sciences over the next 100 years.

Patients and carers invited to join new group helping to shape research and treatment of bones, muscles and joints

Main PPI

Oxford’s newest patient partner group, OPEN ARMS launches today to explore the causes, treatment and care for patients with musculoskeletal conditions. Its first three patient partners explain why they are involved and invite other members of the public to join the team.

NDORMS academics named NIHR Senior Investigators

Main

Congratulations to Professor Jonathan Rees who has been announced as a National Institute of Health Research (NIHR Senior Investigator).