title: Alendronate rescued osteoporotic phenotype in a model of glucocorticoid-induced osteoporosis in adult zebrafish scale.
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.
authors.affiliation: Gruppo Ospedaliero San Donato Foundation, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Pasqualetti
authors.forename: Terenzio
authors.initials: T
authors.lastname: Congiu
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Banfi
authors.forename: Massimo
authors.initials: M
authors.lastname: Mariotti
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D019386:Alendronate / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001857:Bone Matrix / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects*; D004195:Disease Models, Animal; D005938:Glucocorticoids; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D010641:Phenotype; D011239:Prednisolone; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors; D046509:Tissue Culture Techniques; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D005938:Glucocorticoids; D007527:Isoenzymes; D029961:Zebrafish Proteins; D011239:Prednisolone; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D019386:Alendronate
keywords: bone matrix; glucocorticoid-induced osteoporosis; scale; zebrafish