Role Of Osteoglycin In The Linkage Between Fat And Bone

Background:Senile osteoporosis and senile obesity are two major challenges faced by our growing aging society.In the aging process,the number of adipocytes increases and the osteoblasts’decreases in the bone marrow microenvironment,which leading to the net bone loss and becoming the main reason for the senile osteoporosis.Different from the traditional viewpoints,senile osteoporosis and senile obesity are now considered to have many correlations in the pathogenesis,but the specific mechanism is unknown.Identifying new regulators involving in the fat-bone network can broaden our understanding of the two diseases and provide a research basis for developing new therapeutics potentially.Osteoglycin(OGN)is an important part of the extracellular matrix and a new biomarker for cardiovascular diseases and inflammation.Although OGN is highly expressed in fat and in bone,its related function has not been studied.Purposes:This study aimed at strengthening Osteoglycin(OGN)expression to take control of the balance between adipogenesis and osteoblastogenesis in MSCs in vitro and showed the results in a positive effect on bone mass in osteoporosis through decreasing adipogenesis marker Ppary2 expression.Methods:Firstly,differences in capacity of proliferation and specific differentiation in mouse bone mesenchymal stem cells(mMSCs)and senile mouse model-derived bone marrow mesenchymal stem cells(SmMSCs)and the mRNA expression of OGN and Pparγ2 cultured in adipogenic or osteogenic differentiation medium were observed.Secondly,osteogenic abilities of MMSCs and SmMSCs treated with rosiglitazone(a Ppary2 agonist)to induce osteogenic changes were observed,and the negative correlation of Ppary2 with OGN was also evaluated.Thirdly,the role of SmMSCs in promoting osteogenesis was examined through enhancing expression of OGN by Lentivirus plasmid sysem PLJM1-EGFP.Besides,the related mechanism was investigated by the examination of expression of related adipocyte and osteoblast specific genes.Results:Forced OGN expression by OGN-infected lentivirus could increase the expression of Wnt5b,Runx2,OCN,ALP and Co llaland the bone formation,as well as the paralleled decreases of Ppary2 expression,which resulting in the expression inhibition of adipocyte genes such as adipocyte binding protein 2(aP2)in bone marrow and giving rise to increased bone mass.Conclusion:OGN may plays a significant negative role in "fat" bone marrow of the senile osteoporosis and may also provide a potential target for therapeutic intervention of senile osteoporosis characterized by altered differentiation of bone MSCs into osteolasts and adipocytes.