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Inhibition of osteoclastogenesis after bisphosphonate therapy discontinuation: an in vitro approach

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Author(s):
Bradaschia-Correa, Vivian ; Ribeiro-Santos, Giovanna C. ; de Faria, Lorraine Perciliano ; Rezende-Teixeira, Paula ; Arana-Chavez, Victor E.
Total Authors: 5
Document type: Journal article
Source: Journal of Molecular Histology; v. N/A, p. 9-pg., 2022-06-14.
Abstract

Osteoclasts are specialized cells that degrade and resorb bone. Bisphosphonates (BPs) are drugs with well-known capacity to inhibit the resorption of mineralized tissues. Nitrogen-containing BPs, like alendronate (ALN) and zoledronic acid (ZA), inactivate osteoclast activity mostly by alterations on the cytoskeleton architecture of the cell. In this study, we used an in vitro model to test the hypothesis that bisphosphonates may have inhibitory effects on the osteoclastogenesis and osteoclast activity after the therapy was discontinued. Primary osteoclasts were generated from mouse bone marrow in media supplemented with 1,25-dihydroxyvitamin D3 and cultivated over bones pre-treated with ALN and ZA. The pre-saturation of the bone slices with bisphosphonates did not affect cell viability. We found, however, that by disrupting the gene expression of RANKL and OPG the osteoclastogenesis and resorption activity of osteoclasts was significantly disturbed. These inhibitory effects were confirmed by scanning electron microscopy resorption assay, assessment of osteoclast ultrastructure, and by gene expression analysis of TRAP and Cathepsin K. In conclusion, ALN and ZA adhered to the bone matrix reduced the osteoclast activity in vitro. (AU)

FAPESP's process: 13/02240-9 - Analysis of the differentiation and activity of clastic cells cultured over bone, dentin and enamel and treated with bisphosphonates
Grantee:Victor Elias Arana-Chavez
Support Opportunities: Regular Research Grants