Research Of Relationships Between A Novel G Protein-coupled Estrogen Receptor (GPER) And Osteoporosis In Male Mice

Purpose of studyThis study focuses on the mechanism and relationship between GPER and osteoporosis induced by tail-suspended,and the purpose of this study is to provide a novel method for developing new drugs against osteoporosis,as well as curing and preventing male osteoporosis in clinic.Methods1.It is favorable to establish an animal model for studying the diseases,because they could replace human and mimic the pathological state.Tail-suspension is an important way to understand the osteoporosis lead by paralysis,fracture patients and microgravity environment,and fortunately C57 mouse is a good candidate for it.We here designed an instrument for founding animal model of osteoporosis.2.It has been identified that estrogen has anti-osteoporosis effects,but the application on male is still limited application on male.Estrogen has excellent effects against post-menopause osteoporosis,and this process is mediated by classic estrogen receptors.On the basis of tail-suspended model of male mice,we here choosed estrogen and estrogen antagonist to explore the influence on osteoporosis of mice and discussed their underlying mechanisms.3.Male osteoporosis has its own features different from female's.Here we found that GPER and its ligands had no anti-osteoporosis effects,and this process was independent on the classic estrogenic receptors.This conclusion provided the basis of exploring the application of tail-suspension on the osteoporosis model in male mice.We here probed into the relationship between GPER and osteoporosis on male mice.4.Disuse is usual for osteoporosis models in clinic,and spinal cord injury is high-risk and easy to the runoff of bone mass and the metabolism of bone.Former study found that sympathetic nervous could insert the marrow and trabecular bone,and then bind with the ?2 receptor of osteoblasts,modulating the process of bone metabolism.This study found a moderate SCI model on the basis of other studies,and try to observe the relationship between SCI and osteoporosis.Results1.Here we designed a new tail-suspended instrument for mouse according to other papers,we observed and recorded the data of normal and post-tail suspension in male mice,the new model had the feature of steady,quick and high-efficiency.2.In the osteoporosis model of male mice,estrogen sustained bone mass and inhibited bone loss.The subtype of NMDA receptor NR2 A and bone-formation associated factor Runx2,were activated by estrogen,resulting to promoting osteoblasts proliferation and differentiation,and then showed anti-osteoporosis effects.3.GPER and its ligands shows little effect on bone metabolism,but G-15 promote the length of femur by activating the chondrocytes proliferation in the growth plate.The effects of E2 were also showed in this part and this process was induced by classic estrogen receptors but not GPER.4.A moderate SCI model was done by using a forcep-crushing way,G1 could exert neuroprotective effects during the process of SCI,by protecting nervous fibers,alleviating edema of soft tissues and conserving neurons.This process was independent on the estrogen and classic estrogenic receptors.SCI could lead the paralysis of hindlimbs in mice,resulting to the disuse osteoporosis.But this process was complex and not easy to quantify,so SCI was not a good choice for building a standard and easy-quantified osteoporosis model.ConclusionsTail-suspension model of mice is common in disuse osteoporosis,and it is more suitable for studying and observing the changes of osteoporosis animals.In the TS model,E2 exerted excellent anti-osteoporosis effects by the subtype of NMDA receptor,NR2 A.The GPER agonist,G1 could not exert enough effects compared with same dose of E2 in vivo.G15 could promote the proliferation of chondrocytes in the growth plate and length of long bone.On the mice model of SCI,we found that GPER activation could exert estrogen-like effects,leading to motor function recovery induced by SCI,this process was mediated by inhibiting the apoptosis of neurons after SCI.In conclusion,GPER showed excellent neuroprotective but not anti-osteoporosis effect.This study focused on the relationship between the GPER and osteoporosis in male mice,provides us a new way for developing novel anti-osteoporosis drugs and exploring the internal mechanisms of male osteoporosis in the future.