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

Abstract

The biologically active form of vitamin D3, calcitriol (1,25-(OH)2D3), plays a key role in mineral homeostasis and bone formation and dietary vitamin D3 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)2D3 during avian osteogenesis, chicken bone marrow-derived mesenchymal stem cells (BM-MSCs) were exposed to varying doses of 1,25-(OH)2D3 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)2D3 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)2D3 than those from broilers. These data suggest that understanding species and strain specific sensitivities to 1,25-(OH)2D3 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.

Effects of source and level of in ovo-injected vitamin D3 on the hatchability and serum 25-hydroxycholecalciferol concentrations of Ross 708 broilers

“…Vitamin D 3 toxicity in chickens leads to the deposition of calcium in the soft tissues, resulting in renal tubular calcification, reduced performance, and reduced egg production ( NRC, 1987 ; Terry et al., 1999 ). It has been established that elevated levels of 1,25(OH) 2 D 3 can retard mineral deposition and can reduce cell survival and liver function ( Pande et al., 2015 ). In an in vitro study, 2.4 and 24 mmol dosages of 1,25(OH) 2 D 3 resulted in decreased cell proliferation and mineral deposition in chicken bone marrow–derived mesenchymal stem cells ( Pande et al., 2015 ).…”

“…It has been established that elevated levels of 1,25(OH) 2 D 3 can retard mineral deposition and can reduce cell survival and liver function ( Pande et al., 2015 ). In an in vitro study, 2.4 and 24 mmol dosages of 1,25(OH) 2 D 3 resulted in decreased cell proliferation and mineral deposition in chicken bone marrow–derived mesenchymal stem cells ( Pande et al., 2015 ). However, in this study, the in ovo injection of a combination of D 3 and 25OHD 3 at a more moderate but relatively high dosage (4.8 μg) resulted in no negative effects on HI and chick quality as compared with diluent-injected and noninjected control groups.…”

1,25-Dihydroxy vitamin D3 stimulates system A amino acid transport in primary human trophoblast cells

“…It is highly likely that the local concentrations may be much higher due to placental vitamin D production. We have elected not to study higher 1,25-dihydroxyvitmain D3 concentrations than 10 nM because high doses may induce apoptosis (Simboli-Campbell et al, 1996) and decrease cell proliferation (Pande et al, 2015), which may affect placental amino acid transport activity. The effect of 1,25-dihydroxy vitamin D 3 treatment on system L amino acid transporter activity was inconsistent in our study, suggesting that 1,25-dihydroxy vitamin D 3 is not involved in the regulation of system L amino acid transport in PHT cells.…”

Role of 1,25-Dihydroxyvitamin D3 on Osteogenic Differentiation and Mineralization of Chicken Mesenchymal Stem Cells

“…However, there are considerable disagreements of the direct effect of 1,25OHD in osteogenic differentiation and mineralization ( St-Arnaud, 2008 ; Tarroni et al, 2012 ; van Driel and van Leeuwen, 2014 ). In human osteoblasts, 1,25OHD mostly showed stimulatory effects on osteogenic differentiation and mineralization ( Prince et al, 2001 ; Chen et al, 2002 ; Jorgensen et al, 2004 ; Zhou et al, 2006 ; Tourkova et al, 2017 ; Li et al, 2018 ), but with a few exceptions ( Viereck et al, 2002 ); In rat osteoblasts, the responses to 1,25OHD showed either inhibitory effects or no effects ( Harrison et al, 1989 ; Kim and Chen, 1989 ); In mouse osteoblasts, the differentiation and mineralization of osteoblasts showed the most inconstant responses to 1,25OHD with either no effects, inhibition, or facilitation ( van Driel and van Leeuwen, 2014 ; Chen et al, 2016 ; Kim et al, 2016 ; Xiong et al, 2017 ); Limited studies have been done in chicken osteoblasts, but the available data suggested, in general, that 1,25OHD showed an inhibitory effect on osteoblast differentiation and mineralization ( Broess et al, 1995 ; Pande et al, 2015 ). These inconsistent results may be due to various experimental factors, such as species, cell stage, cell origin, treatment time, and dosage, and the presence of extracellular factors in each study ( Czekanska et al, 2012 ; van Driel and van Leeuwen, 2014 ).…”