The Effect of Alendronate on Osteoclastogenesis in Different Combinations of M-CSF and RANKL Growth Factors
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 un...
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MDPI AG
2021-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/3/438 |
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| author | Věra Hedvičáková Radmila Žižková Matěj Buzgo Michala Rampichová Eva Filová |
| author_facet | Věra Hedvičáková Radmila Žižková Matěj Buzgo Michala Rampichová Eva Filová |
| author_sort | Věra Hedvičáková |
| collection | DOAJ |
| description | 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<sup>−6</sup> to 10<sup>−10</sup> 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<sup>−6</sup> M was cytotoxic. Low ALN concentrations of 10<sup>−8</sup> and 10<sup>−10</sup> 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. |
| first_indexed | 2024-03-10T13:10:56Z |
| format | Article |
| id | doaj.art-82ea95dad9894e328df2eb35f9857ec1 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T13:10:56Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-82ea95dad9894e328df2eb35f9857ec12023-11-21T10:45:22ZengMDPI AGBiomolecules2218-273X2021-03-0111343810.3390/biom11030438The Effect of Alendronate on Osteoclastogenesis in Different Combinations of M-CSF and RANKL Growth FactorsVěra Hedvičáková0Radmila Žižková1Matěj Buzgo2Michala Rampichová3Eva Filová4Department of Tissue Engineering, Institute of Experimental Medicine, The Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicDepartment of Tissue Engineering, Institute of Experimental Medicine, The Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicDepartment of Tissue Engineering, Institute of Experimental Medicine, The Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicDepartment of Tissue Engineering, Institute of Experimental Medicine, The Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicDepartment of Tissue Engineering, Institute of Experimental Medicine, The Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicBisphosphonates (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<sup>−6</sup> to 10<sup>−10</sup> 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<sup>−6</sup> M was cytotoxic. Low ALN concentrations of 10<sup>−8</sup> and 10<sup>−10</sup> 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.https://www.mdpi.com/2218-273X/11/3/438alendronateM-CSFosteoclastogenesisRANKL |
| spellingShingle | Věra Hedvičáková Radmila Žižková Matěj Buzgo Michala Rampichová Eva Filová The Effect of Alendronate on Osteoclastogenesis in Different Combinations of M-CSF and RANKL Growth Factors Biomolecules alendronate M-CSF osteoclastogenesis RANKL |
| title | The Effect of Alendronate on Osteoclastogenesis in Different Combinations of M-CSF and RANKL Growth Factors |
| title_full | The Effect of Alendronate on Osteoclastogenesis in Different Combinations of M-CSF and RANKL Growth Factors |
| title_fullStr | The Effect of Alendronate on Osteoclastogenesis in Different Combinations of M-CSF and RANKL Growth Factors |
| title_full_unstemmed | The Effect of Alendronate on Osteoclastogenesis in Different Combinations of M-CSF and RANKL Growth Factors |
| title_short | The Effect of Alendronate on Osteoclastogenesis in Different Combinations of M-CSF and RANKL Growth Factors |
| title_sort | effect of alendronate on osteoclastogenesis in different combinations of m csf and rankl growth factors |
| topic | alendronate M-CSF osteoclastogenesis RANKL |
| url | https://www.mdpi.com/2218-273X/11/3/438 |
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