Abstract
Osteoblasts and adipocytes originate from common mesenchymal progenitor cells and are controlled by specific transcription factors. While 1,25-dihydroxyvitamin D3 (vitamin D) is known to be an important factor for osteoblast differentiation, there are conflicting reports regarding its effect on adipogenesis. In this study, we attempted to understand the effect of exposure of preosteoblasts (MC3T3-E1) to adipogenic media with and without vitamin D and determined the expression of adipogenic genes during this process. Our studies show that while transdifferentiation of preosteoblasts occurred on exposure to adipogenic media, the effect of vitamin D treatment was synergistic resulting in several hundred fold increase in adipocyte transcription factors C/EBPα and peroxisome proliferator-activated receptor-gamma (P < 0.001) along with an increase in markers of adipogenesis and accumulation of lipid droplets in cells. Vitamin D treatment was also accompanied by 100-fold to 700-fold increases in vitamin D receptor expression during the treatment period (P < 0.001). To determine how the effect of vitamin D might compare to other genetic manipulations that promote adipogenic differentiation, we stably knocked down retinoblastoma expression in MC3T3-E1 cells. Recent studies have suggested retinoblastoma (Rb1) tumor suppressor gene function to be critical to maintain osteoblasts function and inhibit adipocyte differentiation. We exposed MC3T3-E1 cells with reduced Rb1 expression to adipogenic media and found an increase in adipogenic differentiation when compared to cells with a full complement of Rb dosage. However, the extent of the change was not as dramatic as seen with vitamin D. These studies show that preosteoblasts are sensitive and respond to these manipulations that favor the adipocytic phenotype. While vitamin D is not known to directly affect targets in adipogenesis, our observations may have resulted from the malleability of preosteoblast genome in MC3T3-E1 cells, which allowed adipocyte specific gene expression under appropriate stimuli. Why this pathway is influenced and subverted by an anabolic bone factor such as vitamin D remains to be determined.
Highlights
Osteoblasts and adipocytes are derived from mesenchymal stem cells, and many studies have suggested the presence of plasticity between these two cell types [1, 2]
Adipocytes and osteoblasts share a common precursor in the bone marrow, and it is known that there is a high degree of plasticity between the two cell lineages [1]
We attempted to understand the influence of adipogenic media with and without vitamin D or the effect of reduction in Rb1 expression on MC3T3-E1cells
Summary
Osteoblasts and adipocytes are derived from mesenchymal stem cells, and many studies have suggested the presence of plasticity between these two cell types [1, 2]. Several studies have suggested the Vitamin D Enhances Adipocytic Differentiation of Osteoblasts occurrence of both osteoblastic and adipocytic phenotype in the same cell population [4]. A preadipocyte cell line has been derived from osteoblastic cell population from mouse calvaria [5]. One of the factors that regulate adipogenesis is peroxisome proliferator-activated receptor-gamma (PPARγ), which belongs to the class of nuclear hormone receptors that are affected by specific ligands such as fatty acids as well as by cross talk with other molecules. PPARγ is both sufficient and necessary for conversion of preadipocytes into adipocytes and is a master regulator of adipogenesis [6]
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