| Background and Purpose Glucocorticoid-induced osteoporosis(GIOP)is a disease in which long-term use of glucocorticoid(GC)causes bone loss,deterioration of bone microstructure and easy fracture.The widespread use of GC has greatly increased the incidence of GIOP.At present,drugs are mainly used in clinical treatment for this disease,but these drugs have certain side effects leading to poor compliance of patients.It is very necessary to find new and effective anti-GIOP drugs with few side effects.According to the theory of traditional Chinese medicine,GIOP is the Yin deficiency of liver and kidney caused by drug pathogens.YGJ has long had significant anti-fatigue,anti-hypoxia,anti-inflammatory and calming effects,and has the effect of nourishing liver and kidney.Some studies have shown that YGJ can protect diseases in liver,kidney,lung and other areas,but no studies have reported its effect on GIOP.Therefore,this paper aims to explore the protective effect of YGJ on GIOP mouse model to elucidate the underlying mechanisms through LC-MS based metabolomics analysis,and to do preliminary experimental research for YGJ to enter clinical research and treatment of GIOP.Methods After 8 weeks of treatment with Dexamethasone(DEX)and YGJ in male C57BL/6J mice,the general condition of the mice was recorded.Bone related parameters and bone morphology were determined by Micro-CT.HE staining was used to observe the pathological changes of bone tissue.Serum levels of bone metabolism markers were detected by ELISA.The liver metabolomics was analyzed to search for the significant markers of anti-GIOP of YGJ and the metabolic pathway affecting it.Results1.The mental state,activity,hair and other conditions of mice were improved after YGJ treatment,and the weight loss caused by DEX could be significantly reversed at the 3rd and 4th week;2.YGJ can increase the number of bone trabecular in the ROI region,and femur shape is more complete and compact under preaxial,level and 3D scanning views.In quantitative analysis of bone trabecular parameters,YGJ significantly improved BMD,BMC,Tb.N,Conn.D,BV/TV,BS/TV,narrowed the bone trabecular space,and reversed bone loss in GIOP mice.3.YGJ can increase the levels of alkaline phosphatase and osteocalcin in serum,and enhance the function of bone formation;4.24 potential markers in GIOP mice induced by YGJ were isolated from liver metabolites,including cortisol,3-hydroxybutyric acid,taurine,esculin and uric acid,which were closely related to osteoporosis,significantly reversed after YGJ treatment.5.Metabolic enrichment pathways involved in YGJ include: Pyruvate metabolism,Steroid hormone biosynthesis,Glycerolipid metabolism,Glycerolphospholipid metabolism,Glycine,Serine and Threonine metabolism,Taurine and Hypotaurine metabolism,etc.;6.The results of pathway topology analysis showed that YGJ had the most significant effect on Taurine and Hypotaurine metabolism,with-log10(P)> 2.0 and Impact > 0.4.Conclusion YGJ reversed bone loss in GIOP mice by regulating alkaline phosphatase and osteocalcin levels to increase bone density and improve bone microstructure.24 potential markers of YGJ anti-Giop mice were isolated from the liver metabolome,including metabolites such as cortisol,3-hydroxybutyric acid,taurine,esculin and uric acid,which are closely related to osteoporosis.The potential metabolic mechanism may be related to the metabolic pathways of Taurine and Hypotaurine metabolism. |
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