Department of Tissue Engineering, Institute of Experimental Medicine, The Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.
Department of Chemistry, Faculty of Science, Humanities and Education, Technical University of Liberec, Studentska 1402/2, 461 17 Liberec, Czech Republic.
Biomolecules. 2021 Mar 16;11(3):438. doi: 10.3390/biom11030438.
Bisphosphonates (BPs) are compounds resembling the pyrophosphate structure. BPs bind the mineral component of bones. During the bone resorption by osteoclasts, nitrogen-containing BPs are released and internalized, causing an inhibition of the mevalonate pathway. As a consequence, osteoclasts are unable to execute their function. Alendronate (ALN) is a bisphosphonate used to treat osteoporosis. Its administration could be associated with adverse effects. The purpose of this study is to evaluate four different ALN concentrations, ranging from 10 to 10 M, in the presence of different combinations of M-CSF and RANKL, to find out the effect of low ALN concentrations on osteoclastogenesis using rat and human peripheral blood mononuclear cells. The cytotoxic effect of ALN was evaluated based on metabolic activity and DNA concentration measurement. The alteration in osteoclastogenesis was assessed by the activity of carbonic anhydrase II (CA II), tartrate-resistant acid phosphatase staining, and actin ring formation. The ALN concentration of 10 M was cytotoxic. Low ALN concentrations of 10 and 10 M promoted proliferation, osteoclast-like cell formation, and CA II activity. The results indicated the induction of osteoclastogenesis with low ALN concentrations. However, when high doses of ALN were administered, their cytotoxic effect was demonstrated.
双膦酸盐（BPs）是一种类似焦磷酸盐结构的化合物。BPs 与骨骼的矿物质成分结合。在破骨细胞进行骨吸收时，含氮的 BPs 被释放并内化，从而抑制了甲羟戊酸途径。结果，破骨细胞无法执行其功能。阿仑膦酸钠（ALN）是一种用于治疗骨质疏松症的双膦酸盐。其给药可能与不良反应有关。本研究的目的是评估四种不同浓度的 ALN（从 10 到 10 M），在不同浓度的 M-CSF 和 RANKL 存在的情况下，观察低浓度 ALN 对大鼠和人外周血单个核细胞破骨细胞生成的影响。根据代谢活性和 DNA 浓度测量来评估 ALN 的细胞毒性作用。通过碳酸酐酶 II（CA II）活性、耐酒石酸酸性磷酸酶染色和肌动蛋白环形成来评估破骨细胞生成的变化。浓度为 10 M 的 ALN 具有细胞毒性。浓度为 10 和 10 M 的低浓度 ALN 促进了增殖、破骨样细胞形成和 CA II 活性。结果表明，低浓度 ALN 可诱导破骨细胞生成。然而，当给予高剂量的 ALN 时，其细胞毒性作用就显现出来了。
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