Zoledronic acid monohydrate (Zoledronate monohydrate) is a third-generation bisphosphonate (BP), with potent anti-resorptive activity. Zoledronic acid monohydrate inhibits the differentiation and apoptosis of osteoclasts. Zoledronic acid monohydrate also has anti-cancer effects[1].
体外研究 (In Vitro)
Zoledronic Acid monohydrate (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 monohydrate increases the expression of osteoclastogenesis supporting factor from MLO-Y4 cells[2]. Zoledronic Acid monohydrate enhances the RANKL expression via IL-6/ JAK2/STAT3 pathway in MLO-Y4 cells[2]. Zoledronic Acid monohydrate inhibits osteoclast differentiation and function through the regulation of NF-κB and JNK signalling pathways[3]. Zoledronic Acid monohydrate (10-100 µM; 1-7 days) markedly reduces the viability of MC3T3-E1 cells[4]. Zoledronic Acid monohydrate (10-100 µM; 1-7 days) induces apoptosis in MC3T3-E1 cells[4]. Zoledronic Acid monohydrate (10-100 µM; 4 days) inhibits cell viability due to the induction of apoptosis[4]. Zoledronic Acid monohydrate exerts inhibitory effects on the differentiation and maturation of MC3T3-E1 cells at concentrations <1 µm[4].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[4]
Cell Line:
MC3T3-E1 cells
Concentration:
0.02 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:
0.02 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:
0.02 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.
体内研究 (In Vivo)
Zoledronic Acid monohydrate (0.05 mg/kg; i.p.; weekly; for 3 weeks) increases bone mineral density and content[5]. Zoledronic Acid monohydrate (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].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
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.
Clinical Trial
分子量
290.10
Formula
C5H12N2O8P2
CAS 号
165800-06-6
中文名称
唑来膦酸一水合物
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
H2O : 14.29 mg/mL (49.26 mM; ultrasonic and adjust pH to 8 with NaOH)
DMSO : < 1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble or slightly soluble)
[1]. Lianwei Wang, et al. Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review. BMC Cancer. 2020; 20: 1059.
[2]. Hyung Joon Kim, et al. Zoledronate Enhances Osteocyte-Mediated Osteoclast Differentiation by IL-6/RANKL Axis. Int J Mol Sci. 2019 Mar; 20(6): 1467.
[3]. Xiao-Lin Huang, et al. Zoledronic acid inhibits osteoclast differentiation and function through the regulation of NF-κB and JNK signalling pathways. Int J Mol Med. 2019 Aug;44(2):582-592.
[4]. XIN HUANG, et al. Dose-dependent inhibitory effects of zoledronic acid on osteoblast viability and function in vitro. Mol Med Rep. 2016 Jan; 13(1): 613-622.
[5]. Samantha Pozzi, et al. High-dose zoledronic acid impacts bone remodeling with effects on osteoblastic lineage and bone mechanical properties. Clin Cancer Res. 2009 Sep 15;15(18):5829-39.