Super pharmacological levels of calcitriol (1,25-(OH)2D3) inhibits mineral deposition and decreases cell proliferation in a strain dependent manner in chicken mesenchymal stem cells undergoing osteogenic differentiation in vitro

超药理水平的骨化三醇(1,25-(OH)2D3)可抑制矿物质沉积,并以菌株依赖性方式降低体外成骨分化的鸡间充质干细胞中的细胞增殖

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作者:Vivek V Pande, Kapil C Chousalkar, Marie S Bhanugopan, Jane C Quinn

Abstract

The biologically active form of vitamin D&sub3;, calcitriol (1,25-(OH)&sub2;D&sub3;), plays a key role in mineral homeostasis and bone formation and dietary vitamin D&sub3;deficiency is a major cause of bone disorders in poultry. Supplementary dietary cholecalciferol (25-hydroxyvitamin D, 25-OH), the precursor of calcitriol, is commonly employed to combat this problem; however, dosage must be carefully determined as excess dietary vitamin D can cause toxicity resulting in a decrease in bone calcification, hypercalcinemia and renal failure. Despite much research on the therapeutic administration of dietary vitamin D in humans, the relative sensitivity of avian species to exogenous vitamin D has not been well defined. In order to determine the effects of exogenous 1,25-(OH)&sub2;D&sub3;during avian osteogenesis, chicken bone marrow-derived mesenchymal stem cells (BM-MSCs) were exposed to varying doses of 1,25-(OH)&sub2;D&sub3;during in vitro osteogenic differentiation and examined for markers of early proliferation and osteogenic induction. Similar to humans and other mammals, poultry BM-MSCs were found to be highly sensitive to exogenous 1,25-(OH)&sub2;D&sub3;with super pharmacological levels exerting significant inhibition of mineralization and loss of cell proliferation in vitro. Strain related differences were apparent, with BM-MCSs derived from layers strains showing a higher level of sensitivity to 1,25-(OH)&sub2;D&sub3;than those from broilers. These data suggest that understanding species and strain specific sensitivities to 1,25-(OH)&sub2;D&sub3;is important for optimizing bone health in the poultry industry and that use of avian BM-MSCs are a useful tool for examining underlying effects of genetic variation in poultry.

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