Aberrant Bone Regulation in Albright Hereditary Osteodystrophy dueto Gnas Inactivation: Mechanisms and Translational Implications

AbstractPurpose of ReviewThis review highlights the impact ofGnas inactivation on both bone remodeling and the development of heterotopic subcutaneous ossifications in Albright hereditary osteodystrophy (AHO). Here we discuss recent advancements in understanding the pathophysiologic mechanisms of the aberrant bone development in AHO as well as potential translational implications.Recent FindingsGnas inactivation can regulate the differentiation and function of not only osteoblasts but also osteoclasts and osteocytes. Investigations utilizing a mouse model of AHO generated by targeted disruption ofGnas have revealed that bone formation and resorption are differentially affected based upon the parental origin of theGnas mutation. Data suggest thatGnas inactivation leads to heterotopic bone formation within subcutaneous tissue by changing the connective tissue microenvironment, thereby promoting osteogenic differentiation of tissue-resident mesenchymal progenitors.SummaryObserved variations in bone formation and resorption based upon the parental origin of theGnas mutation warrant future investigations and may have implications in the management and treatment of AHO and related conditions. Additionally, studies of heterotopic bone formation due toGnas inactivation have identified an essential role of sonic hedgehog signaling, which could have therapeutic implications not only for AHO and related conditions but also for heterotopic bone formation in a wide variety of settings in ...
Source: Current Osteoporosis Reports - Category: Orthopaedics Source Type: research