A rapid, high content,<i>in vivo</i>model of glucocorticoid‐induced osteoporosis

Barrett, Ruth; Chappell, Clare; Quick, Marie; Fleming, Angeleen

doi:10.1002/biot.200600043

Cited by 92 publications

(76 citation statements)

References 41 publications

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“…Excess GC also inhibits osteoblast differentiation and bone nodule formation in bone marrow stroma stem cells [1] , consistent with our previous studies [16] . Furthermore, previous reports indicate that GC induces the inhibition of osteogenesis in zebrafish larvae 21 , consistent with our present results.…”

Section: Discussionsupporting

confidence: 94%

“…Since 2006, when Fleming et al [21] found that wild-type larval zebrafish exposed to prednisolone showed an obvious delay of skull mineralization based on alizarin red staining, zebrafish larvae have been widely used for the highthroughput screen for anti-osteoporotic candidates [22,23] . Tg (sp7:egfp) is a transgenic line zebrafish characterized by the osterix gene driven expression of green fluorescent protein (GFP) in osteoblast differentiation [24,25] .…”

Section: Original Articlementioning

confidence: 99%

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Salvianolic acid B stimulates osteogenesis in dexamethasone-treated zebrafish larvae

et al. 2016

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Aim: Our previous studies show that salvianolic acid B (Sal B) promotes osteoblast differentiation and matrix mineralization. In this study, we evaluated the protective effects of Sal B on the osteogenesis in dexamethasone (Dex)-treated larval zebrafish, and elucidated the underlying mechanisms. Methods: At 3 d post fertilization, wild-type AB zebrafish larvae or bone transgenic tg (sp7:egfp) zebrafish larvae were exposed to Sal B, Dex, or a mixture of Dex+Sal B for 6 d. Bone mineralization in AB strain larval zebrafish was assessed with alizarin red staining, and osteoblast differentiation in tg (sp7:egfp) larval zebrafish was examined with fluorescence scanning. The expression of osteoblastspecific genes in the larvae was detected using qRT-PCR assay. The levels of oxidative stress markers (ROS and MDA) in the larvae were also measured. Results: Exposure to Dex (5-20 μmol/L) dose-dependently decreased the bone mineralization area and integral optical density (IOD) in wild-type AB zebrafish larvae and the osteoblast fluorescence area and IOD in tg (sp7:egfp) zebrafish larvae. Exposure to Dex (10 μmol/L) significantly reduced the expression of osteoblast-specific genes, including runx2a, osteocalcin (OC), alkaline phosphatase (ALP) and osterix (sp7), and increased the accumulation of ROS and MDA in the larvae. Co-exposure to Sal B (0.2-2 μmol/L) dosedependently increased the bone mineralization area and IOD in AB zebafish larvae and osteoblast fluorescence in tg (sp7:egfp) zebrafish larvae. Co-exposure to Sal B (2 μmol/L) significantly attenuated deleterious alterations in bony tissue and oxidative stress in both Dex-treated AB zebafish larvae and tg (sp7:egfp) zebrafish larvae. Conclusion: Sal B stimulates bone formation and rescues GC-caused inhibition on osteogenesis in larval zebrafish by counteracting oxidative stress and increasing the expression of osteoblast-specific genes. Thus, Sal B may have protective effects on bone loss trigged by GC.

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Section: Discussionsupporting

confidence: 94%

Section: Original Articlementioning

confidence: 99%

Salvianolic acid B stimulates osteogenesis in dexamethasone-treated zebrafish larvae

et al. 2016

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“…The data revealed a marked bone loss in larvae treated with prednisolone. Furthermore, this prednisolone-induced bone loss was prevented by RU486, a glucocorticoid receptor (GR) antagonist (Barrett et al 2006). Our present study demonstrates that GIO also occurs in the adult European eel.…”

Section: Cortisol-induced Eel Vertebral Demineralizationsupporting

confidence: 52%

“…Recently, zebrafish larva was proposed as a rapid in vivo model of GIO (Barrett et al 2006) using staining mineralized tissue with fluorescent dye as a method to quantify bone size and density (Du et al 2001). The authors exposed zebrafish larvae in 96-well plates to different doses of GC pharmacological agonist (prednisolone) for 5 days.…”

Section: Cortisol-induced Eel Vertebral Demineralizationmentioning

confidence: 99%

Cortisol mobilizes mineral stores from vertebral skeleton in the European eel: an ancestral origin for glucocorticoid-induced osteoporosis?

Sbaihi

Rousseau

Baloche

et al. 2009

Journal of Endocrinology

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Endogenous excess cortisol and glucocorticoid (GC) therapy are a major cause of secondary osteoporosis in humans. Intense bone resorption can also be observed in other vertebrates such as migratory teleost fish at the time of reproductive migration and during fasting when large amounts of calcium and phosphate are required. Using a primitive teleost, the European eel, as a model, we investigated whether cortisol could play an ancestral role in the induction of vertebral skeleton demineralization. Different histological and histomorphometric methods were performed on vertebral samples of control and cortisoltreated eels. We demonstrated that cortisol induced a significant bone demineralization of eel vertebrae, as shown by significant decreases of the mineral ratio measured by incineration, and the degree of mineralization measured by quantitative microradiography of vertebral sections. Histology and image analysis of ultrathin microradiographs showed the induction by cortisol of different mechanisms of bone resorption, including periosteocytic osteolysis and osteoclastic resorption. Specificity of cortisol action was investigated by comparison with the effects of sex steroids. Whereas, testosterone had no effect, estradiol induced vertebral skeleton demineralization, an effect related to the stimulated synthesis of vitellogenin (Vg), an oviparous specific phospho-calciolipoprotein. By contrast, the cortisol demineralization effect was not related to any stimulation of Vg. This study demonstrates GC-induced bone demineralization in an adult non-mammalian vertebrate, which undergoes natural bone resorption during its life cycle. Our data suggest that the stimulatory action of cortisol on bone loss may represent an ancestral and conserved endocrine regulation in vertebrates.

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“…However, with regard to bone density and quality, dogs appear to be most similar to humans and rats the least (Aerssens et al 1998). Interestingly, in vivo and in vitro bone mineral imaging as well as scale mineralization studies in zebrafish were described as a very simple alternative to explore alterations in mineralization pathways to GC challenge (Barrett et al 2006). …”

Section: Animal Species Used For Gc-induced Osteoporosis Modelsmentioning

confidence: 99%

Animal models to explore the effects of glucocorticoids on skeletal growth and structure

Wood

Souček

Wong

et al. 2018

Journal of Endocrinology

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Glucocorticoids (GCs) are effective for the treatment of many chronic conditions, but their use is associated with frequent and wide-ranging adverse effects including osteoporosis and growth retardation. The mechanisms that underlie the undesirable effects of GCs on skeletal development are unclear, and there is no proven effective treatment to combat them. An in vivo model that investigates the development and progression of GC-induced changes in bone is, therefore, important and a wellcharacterized pre-clinical model is vital for the evaluation of new interventions. Currently, there is no established animal model to investigate GC effects on skeletal development and there are pros and cons to consider with the different protocols used to induce osteoporosis and growth retardation. This review will summarize the literature and highlight the models and techniques employed in experimental studies to date.

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A rapid, high content,in vivomodel of glucocorticoid‐induced osteoporosis

Cited by 92 publications

References 41 publications

Salvianolic acid B stimulates osteogenesis in dexamethasone-treated zebrafish larvae

Salvianolic acid B stimulates osteogenesis in dexamethasone-treated zebrafish larvae

Cortisol mobilizes mineral stores from vertebral skeleton in the European eel: an ancestral origin for glucocorticoid-induced osteoporosis?

Animal models to explore the effects of glucocorticoids on skeletal growth and structure

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