Chronic hyperglycemia affects bone metabolism in adult zebrafish scale model

Abstract

Type II diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia that induce other pathologies including diabetic retinopathy and bone disease. The mechanisms implicated in bone alterations induced by type II diabetes mellitus have been debated for years and are not yet clear because there are other factors involved that hide bone mineral density alterations. Despite this, it is well known that chronic hyperglycemia affects bone health causing fragility, mechanical strength reduction and increased propensity of fractures because of impaired bone matrix microstructure and aberrant bone cells function. Adult Danio rerio (zebrafish) represents a powerful model to study glucose and bone metabolism. Then, the aim of this study was to evaluate bone effects of chronic hyperglycemia in a new type II diabetes mellitus zebrafish model created by glucose administration in the water. Fish blood glucose levels have been monitored in time course experiments and basal glycemia was found increased. After 1 month treatment, the morphology of the retinal blood vessels showed abnormalities resembling to the human diabetic retinopathy. The adult bone metabolism has been evaluated in fish using the scales as read-out system. The scales of glucose-treated fish didn't depose new mineralized matrix and shown bone resorption lacunae associated with an intense osteoclast activity. In addition, hyperglycemic fish scales have shown a significant decrease of alkaline phosphatase activity and increase of tartrate-resistant acid phosphatase activity, in association with alterations in other bone-specific markers. These data indicates an imbalance in bone metabolism, which leads to the osteoporotic-like phenotype visualized through scale mineral matrix staining. The zebrafish model of hyperglycemic damage can contribute to elucidate in vivo the molecular mechanisms of metabolic changes, which influence the bone tissues regulation in human diabetic patients.

Craniofacial skeleton of MEXICAN tetra (Astyanax mexicanus): As a bone disease model

“…Moreover, they found that the transgenic homologous zebrafish has a reduction in scale size. This has been reported in other zebrafish type 1 diabetes models as well (Carnovali et al, ; Riddle et al, ). Neither of these studies have specifically looked into the rest of the skeletal structures.…”

Uptake of osteoblast-derived extracellular vesicles promotes the differentiation of osteoclasts in the zebrafish scale

“…The zebrafish scale is a thin membranous bone embedded in the skin that consists of OBs, OCs, and bone matrix. Although the structure of zebrafish scales is rather simple compared with mammalian bones [3][4][5] , various in vivo and in vitro studies have demonstrated that OCs and OBs in teleost scales respond to hormones and other substances as one would predict from observation of the mammalian bone [6][7][8][9][10][11][12] , indicating that fundamental cellular and molecular programs that regulate OCs and OBs are highly conserved amongst vertebrates. In addition, this "surface" bone tissue enables in vivo live-imaging of OCs and OBs using fluorescent transgenic lines.…”

Fish scale is a suitable model for analyzing determinants of skeletal fragility in type 2 diabetes

“…In the study by Carnovali et al [18], the authors introduced a new model for studying glucose and bone metabolism. Using the scales of zebrafish, a suitable model, Carnovali et al [18] examined the effect of hyperglycemia on bone metabolism.…”