The Roles Of LRPs In Skeletal Development And Bone

Osteoporosis is a major global public health problem for adultsespecially over age55years.According to the statistics,every year it costbillions of Euros/Dollars in Osteoporosis and osteoporotic fractures.Several years of studies demostrated that the Wnt signaling was a centralregulator of skeletal modeling and remodeling. LRP4、LRP5and LRP6arethe members of the low-density lipoprotein-related receptors (LRPs) familyas Wnts co-receptors with an important role in osteogenesis. Loss-orgain-of-function mutations in two Wnt co-receptors, LRP5and LRP6, havedrawn attention to the importance of the Wnt pathway in skeletaldevelopment and Bone.LRP4is a novel osteoblast expressed Dickkopf1（DKK1） and sclerostin receptor with a physiological role in theregulation of bone growth, which is likely mediated through its function asan integrator of Wnt and Bone morphogenetic proteins (BMPs) signalingpathways. The Wnt pathway has rapidly emerged as a therapeutic target fordrug discovery. Neutralizing antibodies and small-molecule inhibitors ofendogenous Wnt inhibitors have been shown early promise as boneanabolic agents， including the antibodies of DKK1and sclerostin.However, the Wnt pathway could have an effect on extraskeletal tissues andcome the potential adverse events, considerable work will be needed to ensure the safety of these new therapies. This review summarizes thestructural feature of LRPs，including LRP4、LRP5and LRP6，and ourcurrent understanding of the Wnt pathway operates on bone and skeletalphysiology and drug discovery.These studies showed that LRPs have a veryimportant role in regulating bone and is a new target for treatingOsteoporosis.