Zoledronic Acid (Zoledronate) disodium tetrahydrate is a potent third-generation bisphosphonate (BP), exhibiting strong anti-resorptive activity. It effectively inhibits osteoclast differentiation and apoptosis, while also demonstrating anti-cancer properties [1].
体外活性
Zoledronic Acid disodium tetrahydrate (0.1-1 μM; 48 hours) increases receptor activator of nuclear factor kB ligand (RANKL) and sclerostin mRNA expressions in osteocyte-like MLO-Y4 cells [2]. Zoledronic Acid disodium tetrahydrate increases the expression of osteoclastogenesis supporting factor from MLO-Y4 cells [2]. Zoledronic Acid disodium tetrahydrate enhances the RANKL expression via IL-6/ JAK2/STAT3 pathway in MLO-Y4 cells [2]. Zoledronic acid disodium tetrahydrate inhibits osteoclast differentiation and function through the regulation of NF-κB and JNK signalling pathways [3]. Zoledronic Acid disodium tetrahydrate (10-100 μM; 1-7 days) markedly reduces the viability of MC3T3-E1 cells and induces apoptosis in MC3T3-E1 cells [4]. Zoledronic Acid disodium tetrahydrate (10-100 μM; 4 days) inhibits cell viability due to the induction of apoptosis [4]. Zoledronic Acid disodium tetrahydrate exerts inhibitory effects on the differentiation and maturation of MC3T3-E1 cells at concentrations <1 μM [4]. Cell Viability Assay [4] Cell Line: MC3T3-E1 cells Concentration: 0.01 μM, 0.1 μM, 1 μM, 10 μM, 100 μM Incubation Time: 1 day, 3 days, 5 days, 7 days Result: Reduced cells viability at 10 μM and 100 μM. Apoptosis Analysis [4] Cell Line: MC3T3-E1 cells Concentration: 0.01 μM, 0.1 μM, 1 μM, 10 μM, 100 μM Incubation Time: 1 days, 4 days, 7 days Result: Increased the number of early apoptotic cells and late apoptotic or necrotic cells at dose-dependent and time-dependent (high concentrations). Western Blot Analysis [4] Cell Line: MC3T3-E1 cells Concentration: 0.01 μM, 0.1 μM, 1 μM, 10 μM, 100 μM Incubation Time: 4 days Result: Down-regulated the protein level of inactive caspase-3 and up-regulated the protein level of active caspase-3 at the concentrations of 10 and 100 μM.
体内活性
Zoledronic Acid disodium tetrahydrate (0.05 mg/kg; i.p.; weekly; for 3 weeks) increases bone mineral density and content [5]. Zoledronic Acid disodium tetrahydrate (0.5-1 mg/kg; i.p.; weekly; for 3 weeks) inhibits both osteoclast and osteoblasts function and bone remodeling in vivo interfering with bone mechanical properties [5]. Animal Model: Five-week-old C57BL6 mice [5] Dosage: 0.05 mg/kg, 0.5 mg/kg, 1 mg/kg Administration: Intraperitoneal injection, weekly, for 3 weeks Result: Inhibited both osteoclast and osteoblasts function and bone remodeling at 0.5 mg/kg and 1 mg/kg.
