| Objective: Osteoporosis is a chronic metabolic disease that decrease the living quality of the elderly.To explore the underlying molecular biological mechanisms that involved into the pathological process could provide theoretical support to clinical treatments.Basic studies have suggested that the Sirtuins family could regulate bone metabolism.Among members of Sirtuins,the expression of Sirt2(Sirtuin 2)is the highest.However,the impact of Sirt2 on bone metabolism remains unknown.We thus aim to explore the effect of Sirt2(Sirtuin 2)on microstructures,biomechanics of rat bone,and the effect of Sirt2 inhibitor AGK2 during the process of rat bone marrow-derived macrophage differentiating to osteoclasts.Methods: Extract the thigh bone and tibias from 20-week old SD wild type(WT)rats and Sirt2 knock out(KO)rats respectively,taking micro-computed tomography scan(micro CT)and three-point bending test.Extract bone marrow-derived monocytes and macrophages(BMM),adding Sirt2 inhibitor AGK2.Induce the primary cells to differentiate into osteoclasts for 7 days,after which detecting specific differentiation makers of osteoclasts.Results: Compared with WT SD rats,the BMD(bone mineral density)(WT: 336.36±41.90,Sirt2 KO: 444.36±79.16),BV/TV(%)(WT: 7.66±3.42,Sirt2 KO: 12.67±5.60)and Tb.N(WT: 2.95±0.46,Sirt2 KO: 3.51±0.61)of Sirt2 KO rats improved remarkably;Elasticity modulus(WT: 6.65±1.32,KO: 10.90±4.46),bending stiffness(WT: 21.74±4.67,KO: 30.85±60.48)and rupture energy(WT: 39.39±12.37,KO: 61.84±19.66)of Sirt2 KO rats also improved.The differentiation ability of BMMs to osteoclasts decreased in the adding AGK2 group,meanwhile the levels of specific differentiation biomarkers of osteoclasts such as ITGαv,TRAP,NFATc1 and RANK decreased.Conclusion: Sirt2 KO could improve the BMD and quality of rat bone.AGK2,the inhibitor of Sirt2,could decrease the differentiation capability of rat BMM to osteoclasts.Objective: The present study undertakes to investigate the relationships among sex hormone-binding globulin(SHBG)and sex hormones including follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),testosterone(TT),free testosterone(FT)with bone mineral densities(BMDs)and 10-year probability of major osteoporosis fractures(MOF)and hip fracture(HF)in Chinese type 2 diabetes mellitus(T2DM)patients.Methods: In this cross-sectional study,a total of 785 patients(498 men,287 women)with T2 DM were enrolled.BMDs at lumbar spine(L2-4),femoral neck(FN)and total hip(TH)were measured by dual-energy X-ray absorptiometry(DXA).The 10-year probability of fractures was accessed by Fracture Risk Algorithm(FRAX)tool.Serum levels of sex hormones and SHBG were tested simultaneously.Linear regression analysis and Logistic regression analysis were used to evaluate the relationships among sex hormones and BMDs,MOF and HF.Results: In male patients,FSH and E2 were determinants of BMDs at L2-4(FSH,beta =-0.177,P < 0.05;E2,beta = 0.158,P < 0.05),E2 was determinant of FN(beta = 0.136,P < 0.05)and TH(beta = 0.130,P < 0.05);FSH was the contributor of MOF(beta = 0.243,P < 0.001)and HF(beta = 0.197,P < 0.001).Whereas in female patients,E2 was the major contributor of BMDs at L2-4(beta = 0.183,P < 0.05),FN(beta = 0.123,P < 0.05)and TH(beta = 0.122,P < 0.05);E2 contributed to MOF(beta =-0.156,P < 0.05)and HF(beta =-0.168,P < 0.05).Conclusion: Males with T2 DM who had higher levels of serum FSH and lower levels of serum E2 tended to have lower BMDs and higher fracture risks evaluated by FRAX.Females with T2 DM who had lower levels of serum E2 tended to have lower BMDs and higher fracture risks.The variations of sex hormones were helpful in indication of BMD changes and future fracture risks. |
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