F2r, also known as Coagulation Factor II Thrombin Receptor, is an important member of the G-protein-coupled receptor (GPCR) family. It plays a role in regulating blood clotting through protein hydrolytic cleavage-mediated receptor activation. It is also involved in various signaling pathways such as the Akt and NFκB signaling pathways, and is highly expressed in osteoclasts [1,2].

In studies on osteoclasts, loss-of-function experiments using F2r-targeted short hairpin RNA (sh-F2r) lentivirus in mouse bone marrow cells (MBMs) induced osteoclasts showed that F2r knockdown led to a significant increase in osteoclast activity, number, size, promoted bone resorption and F-actin ring formation with increased osteoclast marker gene expression. In contrast, overexpression of F2r blocked osteoclast formation, maturation, and acidification, indicating that F2r negatively regulates osteoclast formation and function. The mechanism may be through inhibiting the F2r-Akt and F2r-NFκB signaling pathways in response to RANKL stimulation [1].

In conclusion, F2r has a negative regulatory function on osteoclastogenesis, mainly by inhibiting the Akt and NFκB signaling pathways. These findings from mouse model-based research provide potential new therapeutic approaches for bone diseases such as osteoporosis [1].