Kiss1 Regulates Bone Mass

Bone remodeling is balanced by the bone formation of osteoblasts and bone resorption of osteoclasts.Kisspeptin,encoded by Kissl,triggers onset of puberty through binding to its receptor-GPR54.A significant feature during this period is bone development.Our previous study of GPR54 can greatly affect osteoclast activity,suggesting that this ligand/receptor system may play an important role in bone environment.In order to make fully understand of this system in bone metabolism,we explored Kiss1 together with Gpr54 in our study.We examined pHenotype of Kiss1 Gene knockout mice,the mice showed great bone loss,which is similar to Gpr54 Gene knockout mice.Osteoclast activity was enhanced both in vivo and in vitro of Kissl knockout mice.Respectively,osteoclast was inhibited when activation of Gpr54.A large number of activated osteoclast appeared when co-cultured with Kiss1-/-osteoblasts by altering the RANKL/OPG ratio;In addition,the osteoblasts proliferation,differentiation and mineralization were enhanced both in vivo and in vitro in Kiss1 and Gpr54 knockout mice;Further,we found Gpr54 regulate osteoclast activity may through PLC/PKC mediated DUSP18 activation.DUSP18 may affect osteoblasts by deregulation of RUNX2.RANKL,the downstream of RUNX2,was also down regulated,that will cause suppression of osteoclasts;In addition,the chimeric mice showed that loss of Gpr54 appeared bone mass decrease;finally,we treated OVX mice with the ligand of GPR54,called Kp-10,bone mass were significant increased after treatment.In conclusion,our study demonstrates that Kisspeptin can affect osteoclasts and osteoblasts,surppress osteoclast activity dramaticly,and shows great potential therapeutic drug for osteolytic bone lesions.