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Carmen Corciulo, Göteborgs universitet, 75 000 kronor

Bakgrund och motivering

Osteoarthritis (OA) is more common and painful in post-menopausal women compared to age-matched men. During menopause, estradiol stabilizes at low concentrations. Estradiol has been reported to regulate the expression of the receptors for adenosine, an endogenous molecule. The molecular pathways, activated by adenosine and estrogens, affect chronic pain. Understanding this interaction and its therapeutic potential is the main goal of the proposed project.

Syfte och mål

Pain in OA is a complex phenomenon, attributable to different independent mechanisms: inflammation of the synovium, bone resorption, and innervation of the bone.

The project aims to determine whether:

• postmenopausal women with OA have lower levels of adenosine and estrogens in the blood and in the joint;
• estrogens inhibit inflammation in the synovial membrane of OA patients;
• postmenopausal women have altered microarchitecture of the bone and bone innervation;
• estrogens replacement and block of the adenosine molecular pathway could be a new therapeutic strategy for treating OA in a mouse model.

Metod

The research plan includes the collection of blood, synovial fluid and synovial membrane biopsies from OA patients along with their clinical information. The purpose is to identify sex differences in the concentration of estrogens and adenosine in the joint and their correlation with clinical parameters. Knee joints will also be collected from OA patients undergoing surgery for knee replacement. Innervation and alteration on the bone will be analyzed in correlation with the clinical parameters and pain score. The project also aims to test the therapeutic efficacy of a combined treatment of estrogen and adenosine receptor antagonist in pain reduction and disease progression on an OA animal model.

Betydelse för patienten 

Musculoskeletal disorders are highly prevalent and are associated with the highest number of years lived with disabilities. Among them, OA is the second-largest contributor. Women have an increased risk of developing OA compared to men. A better understanding of this sex difference is needed and it will help to identify new and efficient therapeutic approaches for improving or delay the outcome of OA. The proposed project will provide a significant contribution towards that goal by clarifying whether estrogen-mediated regulation of adenosine receptors can be utilized for the development of new treatments for patients with OA.