The purpose of one of the research objectives was to test the hypothesis that combining treatment with a modulator of the adenosine signaling and estradiol is an effective strategy against disease progression in an OA mouse model.
A pilot study was performed to find the proper dose of estradiol able to mimic the physiological concentration of the steroid hormone without important side effects in the whole body. For this purpose, ovaries were removed from female mice (OVX mice) to lower the endogenous level of sex hormones. Then, two doses of estradiol were administered every 3 days for 8 weeks and the effect of the hormone in different organs was measured every 2 weeks. The dose of estradiol resembling the physiological level of the hormone on bone was chosen for the following experiments. Data from the pilot study were shared with the scientific community through a peer-review publication and an open-access repository.
The effect of ovary removal and subsequent reduction of sex hormones was tested on an OA mouse model. Data shows that estradiol replacement in OVX mice reduces cartilage and bone damage, lower joint inflammation, and improves motor ability and pain sensitivity. Moreover, the number of T cells in the inguinal lymph nodes, which drains the knee, decreased in OVX mice treated with estradiol. These results were presented at the 2022 OARSI World Congress on Osteoarthritis (Berlin, 6-10 April 2022) and published on a peer-reviewed journal.
In the latest experiment, I tested the effect of a modulator of the adenosine signaling on OVX and control OA mice after 8 and 12 weeks of treatment. Data have been collected and a manuscript is in preparation.
The study of the molecular interaction of estradiol-adenosine signaling in T cells is ongoing.
The implementation of the project together with the participation in meetings and training courses allow me to acquire technical abilities, pedagogical knowledge, and leadership skills.
