Long-term effects of glucocorticoid treatment in humans induce bone loss and increase the risk of fracture in the skeleton. The pathogenic mechanisms of glucocorticoid-induced osteoporosis (GIOP) are still unclear. The GIOP and its effects have been reproduced in several animal models including Danio rerio (zebrafish) embryo. The treatment of adult fish with prednisolone (PN) has shown a dose-dependent decrease of mineralized matrix in the scales. Large resorption lacunae are characterized by single TRAP-positive cells which migrate to the margin of the scale merging into a multinucleated structures. The treatment with PN of cultured scales did not increase TRAP activity suggesting that the massive presence of osteoclasts in the resorption sites could be likely the result of a systemic recruitment of monocyte-macrophage precursors. We observed that treatment with PN induced a significant decrease of the alkaline phosphatase (ALP) activity in scale scleroblasts if compared with untreated controls. Then, we investigated the total mineral balance under prednisolone treatment using a time-dependent double live staining. The untreated fish fully repaired the resorption lacuna induced by prednisolone, whereas treated fish failed. The presence of osteoclast resorption fingerprints on new matrix suggested that the osteoclast activity counterbalances the osteodepositive activity exerted by scleroblasts. The treatment with PN in association with alendronate (AL) has surprisingly resulted in a significant decrease of TRAP activity and increase of ALP compared to PN-treated fish in biochemical and histological assays confirming the action of alendronate against GIOP in fish as well in humans.

Alendronate rescued osteoporotic phenotype in a model of glucocorticoid-induced osteoporosis in adult zebrafish scale / S. Pasqualetti, T. Congiu, G. Banfi, M. Mariotti. - In: INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY. - ISSN 0959-9673. - 96:1(2015), pp. 11-20.

Alendronate rescued osteoporotic phenotype in a model of glucocorticoid-induced osteoporosis in adult zebrafish scale

M. Mariotti
Ultimo
2015

Abstract

Long-term effects of glucocorticoid treatment in humans induce bone loss and increase the risk of fracture in the skeleton. The pathogenic mechanisms of glucocorticoid-induced osteoporosis (GIOP) are still unclear. The GIOP and its effects have been reproduced in several animal models including Danio rerio (zebrafish) embryo. The treatment of adult fish with prednisolone (PN) has shown a dose-dependent decrease of mineralized matrix in the scales. Large resorption lacunae are characterized by single TRAP-positive cells which migrate to the margin of the scale merging into a multinucleated structures. The treatment with PN of cultured scales did not increase TRAP activity suggesting that the massive presence of osteoclasts in the resorption sites could be likely the result of a systemic recruitment of monocyte-macrophage precursors. We observed that treatment with PN induced a significant decrease of the alkaline phosphatase (ALP) activity in scale scleroblasts if compared with untreated controls. Then, we investigated the total mineral balance under prednisolone treatment using a time-dependent double live staining. The untreated fish fully repaired the resorption lacuna induced by prednisolone, whereas treated fish failed. The presence of osteoclast resorption fingerprints on new matrix suggested that the osteoclast activity counterbalances the osteodepositive activity exerted by scleroblasts. The treatment with PN in association with alendronate (AL) has surprisingly resulted in a significant decrease of TRAP activity and increase of ALP compared to PN-treated fish in biochemical and histological assays confirming the action of alendronate against GIOP in fish as well in humans.
Bone matrix; Glucocorticoid-induced osteoporosis; Scale; Zebrafish; Acid Phosphatase; Alendronate; Alkaline Phosphatase; Animals; Biomarkers; Bone Density Conservation Agents; Bone Matrix; Bone Remodeling; Disease Models, Animal; Isoenzymes; Male; Osteoclasts; Osteoporosis; Phenotype; Tartrate-Resistant Acid Phosphatase; Time Factors; Tissue Culture Techniques; Zebrafish; Zebrafish Proteins; Glucocorticoids; Prednisolone; 2734; Molecular Biology; Cell Biology
Settore MED/04 - Patologia Generale
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/463644
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