The roles of adenosine and adenosine receptors in bone remodeling.

Adenosine regulates a wide variety of physiological processes including heart rate, vasodilation and inflammation through the activation of specific cell surface adenosine receptors. In addition to these well-established roles of adenosine, recent genetic and pharmacological research has implicated adenosine as an important regulator in bone remodeling. The secretion of adenosine and the presence of its four receptors in bone cells have been well documented. More recently, we provided the first evidence that adenosine regulates osteoclast formation and function through A1 receptor (A1R), and showed that A1R-knockout mice have significantly increased bone volume as a result of impaired osteoclast-mediated bone resorption. Moreover, adenosine A1R-knockout mice are protective from boss loss following ovariectomy further supporting the involvement of adenosine in osteoclast formation and function. This short review summarizes current knowledge related to the roles of adenosine and adenosine receptors in bone formation and remodeling. A deeper insight into the regulation of bone metabolism by adenosine receptors should assist in developing new therapies for osteoporosis.