Targeting estrogen and adenosine receptors cross-talk for osteoarthritis treatment

The high incidence of osteoarthritis (OA) in post-menopause women suggests that estrogen decline is a possible trigger of the OA pathogenesis.

The goal of the proposed project is to characterize the interaction in T-cells between estrogens and adenosine receptors (A2AR and A2BR, involved in the regulation of inflammatory mechanisms), and test whether the inhibition of this interaction could be targeted to improve OA symptoms.

The project includes three specific aims:AIM 1: To define the effect of estrogens on the expression and function of the pro-inflammatory A2B adenosine receptor and on the anti-inflammatory A2A adenosine receptor in isolated murine T-lymphocytes;AIM 2: To determine whether estrogen has a protective effect on osteoarthritis progression in female mice lacking A2A adenosine receptor;AIM 3: To test the combined treatment with 17β-estradiol and the A2B adenosine receptor antagonist on pain reduction and disease progression in an osteoarthritis mouse model.The work plan includes in-vitro experiments by using techniques of molecular biology, research in-vivo and ex-vivo by using an osteoarthritis mouse model, imaging techniques, immunohistochemistry, motor and pain tests.

The proposed project is focused on the inflammatory component of OA challenging the previous definition of OA as a disease with a little and non-significant inflammatory component. In addition, the urgent need for an efficacious therapy for OA underlies the importance of my project.