Effects and mechanisms of oridonin on ovariectomy-induced bone loss in rats
Objective To investigate the effects of Oridonin(ORI)on bone tissue pathology,microstructure,and potential mechanisms in an ovariectomized(OVX)rat model of osteoporosis.Methods Female Sprague-Dawley(SD)rats aged 8 weeks were randomly assigned to Sham,OVX+vehicle(Veh),and OVX+ORI groups.The OVX+ORI group received intraperitoneal injections of 0.1％Oridonin at 2 mg/kg twice weekly,and the OVX+Veh group received an equivalent volume of sterile water injections,both for a duration of 12 weeks.Blood plasma and bone tissue specimens were collected from all groups.Bone tissue staining sections were used to observe pathological changes.Micro computed tomography(Micro-CT)scans were conducted to assess bone microstructure and bone mineral density(BMD).The mRNA levels of Osteoprotegerin-Receptor Activator of NF-KB-Receptor Activator of NF-κB Ligand(OPG-RANKL-RANK)signaling pathway and Wnt/β-Catenin signaling pathway-related proteins in bone tissue were measured using polymerase chain reaction(PCR).The expression of these signaling pathway-related proteins was evaluated using Western blotting.Bone metabolism markers in blood plasma were as-sessed using the enzyme linked immunosorbent assay(ELISA).Independent sample t-test wasused for comparisons between two groups.Results Compared to the OVX+Veh group,the OVX+ORI group ex-hibited significantly reduced trabecular fractures and improved integrity.The levels of RANKL,sclerostin(SOST),c-terminal telopeptide of type Ⅰ collagen(CTX)and tartrate resistant acid phosphatase(TRAP)in the OVX+Veh group were higher than those in the OVX+ORI group[1.62±0.04 vs.1.02±0.06,t=26.766,P＜0.01;1.60±0.04 vs.1.08±0.04,t=29.898,P＜0.01;(61.68±6.88)vs.(28.97±4.07)ng/ml,t=12.937,P＜0.01;(759.44±32.47)vs.(435.71±31.43)pg/ml,t=22.654,P＜0.01].The levels of bone mineral density(BMD),OPG,wnt3a,β-Catenin,low-density lipoprotein receptor-related protein 5(LRP5),alkaline phosphatase(ALP)and procollagen Ⅰ N-terminal propeptide(PINP)in the OVX+Veh group were significantly lower than those in the OVX+ORI group[(96.75±8.44)vs.(195.84±13.16)mg/cm3,t=-20.036,P＜0.01;0.56±0.04 vs.1.00± 0.05,t=-21.267,P＜0.01;0.31±0.01 vs.0.93±0.04,t=-52.286,P＜0.01;0.31±0.01 vs.1.02±0.07,t=-30.535,P＜0.01;0.32±0.03 vs.1.00±0.03,t=-50.398,P＜0.01;(15.71±3.44)vs.(53.21±6.99)ng/ml,t=-15.229,P＜0.01;(23.83±3.54)vs.(63.95± 4.17)ng/ml,t=-23.217,P＜0.01].Conclusion Oridonin may exert its effects by inhibiting the OPG-RANKL-RANK signaling pathway,while concurrently upregulating the Wnt/β-Catenin signaling path-way.These combined effects contribute to the mitigation of ovariectomy-induced bone loss,reduction of bone microstructural damage in rats.
OridoninOsteoporosisOsteoprotegerin-receptor activator of NF-κB-receptor acti-vator of NF-κB ligand signaling pathwayWnt/β-catenin signaling pathway
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