RESUMO
Diabetes mellitus (DM),a highly prevalent chronic metabolic disorder,can damage multiple organ systens.For instance,in the skeletal system,DM can lead to osteoporosis,delayed fracture healing or nonunion of fractures,which not only affects the prognosis of bone diseases and quality of life but also leads to huge medical and economic burden.The main reason of these skeletal complications is the disruption of the balance between bone formation and bone resorption,which leads to the disorders of bone metabolism.The mechanism of bone metabolism disorders in DM patients is determined by many biological factors,including high glucose (HG),oxidative stress,accumulation of advanced glycation end products (AGEs),insulin levels,inflammatory factors,growth factors,adipocytokines and hypaglycemic agents.Furthermore,as an important feature of DM,HG has obvious effects on bone metabolism mainly by acting on signal transduction pathways,including PI3K/Akt pathway,cAMP/PKA pathway,wnt pathway,MARK pathway,AMPK/mTOR/ULK1 pathway,BMP pathway,EphrinB2/EphB4 pathway,PPARγ pathway and NF-κB pathway.The above mentioned signal pathways regulate the proliferation,differentiation,apoptosis and aging of cells,such as bone marrow mesenchymal stem cells (BMSCs),osteoblasts and osteoclasts.These research areas have become the current hotspot for investigation.Although some studies has been conducted in these research areas,several limitations are still exist especially in vivo study.Thus,further studies are required.The present article reviews the effects of HG on bone metabolism signaling pathways.The purpose of this review is conducive to further understand the molecular mechanism of bone metabolism regulated by HG,and to provide theoretical basis and orientations for prevention and treatment of diabetic bone diseases.
RESUMO
Objective To investigate the effects of sodium butyrate on the activity of RAW264.7 cells and the osteoclast differentiation.Methods The RAW264.7 cells were treated by sodium butyrate at concentrations of 0,0.25,0.50,1.00,2.00,3.00,4.00 and 5.00 mmol/L,with 3 double pores for each concentration.The cytotoxicity of sodium butyrate on RAW264.7 cells was detected by a CCK-8 kit.The effects of sodium butyrate (0,0.25,0.50 and 1.00 mmol/L) on apoptosis of RAW264.7 cells were detected by Hoechst33342 staining.RAW264.7 cells were induced into osteoclasts by osteoclast differentiation factors.The experiment was carried out in 2 groups (n =3).After induced maturation,the experimental group was treated with 1.00 mmol/L sodium butyrate and the control medium was added only with the same volume of solvent.The number of osteoclasts and the area of bone resorption were observed and compared.The differentiation of RAW264.7 cells was detected by tartrate-resistant acid phosphatase (TRAP) staining.Western blotting was used to detect the effects of sodium butyrate (0,0.25,0.50 and 1.00 mmol/L) on NF-κB-related signaling pathway in RAW264.7 cells.Results Compared with the group of 0 mmol/L sodium butyrate,the activity of cells treated with 1.00,2.00,3.00,4.00 and 5.00 mmol/L sodium butyrate for 24 h was significantly decreased (P ＜ 0.05).Treatment with 1.00 mmol/L sodium butyrate for 24 h induced apoptosis.The number of osteoclasts in the control group and the experimental group were 9.33 ± 2.08 and 4.67 ± 1.16,respectively,showing a significant difference between the 2 groups (t =3.395,P =0.027).The percentages of bone resorption area in the control group and the experimental group were 52.43％ ± 5.38％ and 14.28％ ± 2.72％,respectively,also showing a significant difference between the 2 groups (t =10.970,P ＜ 0.001).Western blot results showed that,compared with other concentrations of sodium butyrate,treatment with 1 mmol/L sodium butyrate on RAW264.7 cells for 24 h led to an increase in the expression levels of cytoplasmic p65,B lymphoma-2 associated X protein and cleaved-caspase 3 and the acetylation of Histone H3 but a decrease in the phosphorylation level of α/β subunit of NF-κB kinase.Conclusions With the increased concentration of sodium butyratecan,the activity of NF-κB may be suppressed and the number of apoptotic cells may increase.1.00 mmol/L sodium butyrate can reduce osteoclast formation and bone resorption area.
