Identification and cloning of a human urea transporter HUT11, which is downregulated during adipogenesis of explant cultures of human bone

Abstract

Bipotential cells in human trabecular bone explant cultures that express osteoblast characteristics are able to undergo adipogenesis in the presence of 3-isobutyl-1-methylxanthine plus dexamethasone (Nuttall et al. [1998] J Bone Miner Res 13:371-382). The initial studies of these bipotential cells in explant cultures have been extended to examine differential gene expression during osteoblast/adipocyte transdifferentiation. Using differential display, we have identified a gene expressed in trabecular bone explant cultures that is downregulated as these cells differentiate from an osteoblast to an adipocyte phenotype. Homology searching identified this gene as the human urea transporter HUT11. The expression and downregulation of HUT11 have been observed in multiple patient bone explant cultures. The size of the bone explant-derived HUT11 mRNA is approximately 4.4 kb, which is identical to the largest splice variant reported. In this article, we report the cloning and sequencing of this gene from primary human osteoblasts. In addition, we report tissue distribution for the bone explant-derived form of HUT11 mRNA and show a reciprocal relationship between the expression of HUT11 and the nuclear hormone receptor peroxisome proliferator-activated receptor gamma 2, which is a marker of adipocyte differentiation. Because the control of osteoblast/adipocyte transdifferentiation is unknown, selective downregulation of HUT11 during adipogenesis suggests that HUT11 expression may be a marker of the switch from an osteoblast to an adipocyte phenotype. Understanding the role of HUT11 in osteoblasts may provide insights into the mechanism controlling osteoblast and adipocyte differentiation.

Expression of blood group genes by mesenchymal stem cells

“…Prichett et al (2000) detected the human urea transporter HUT11 (SLC14A1; JK), the protein carrying the Jk antigen, in ‘explant cultures of human bone’ containing osteoblasts and an unknown fraction of MSCs. We confirmed a reduced SLC14A1 (JK) transcription in differentiating MSCs.…”

Coexpression of osteogenic and adipogenic differentiation markers in selected subpopulations of primary human mesenchymal progenitor cells

“…Clinical observations and in vitro models document an inverse relationship between bone marrow adipocytes and osteoblasts [Bennett et al, 1991;Oreffo et al, 1997;Thompson et al, 1998; Prichett et al, 2000;Justesen et al, 2001;Abdallah et al, 2004;Nuttall and Gimble, 2004]. However, previous data reported by Garcia et al [2002] using murine neonatal calvaria-derived cells indicated that the expression level of several adipocyte markers changed in the time-course of osteoblast maturation in parallel with the expression of a set of osteoblast markers.…”

“…A number of in vitro studies support the hypothesis that a high degree of plasticity exists between adipocytic and osteoblastic pathways [Bennett et al, 1991;Oreffo et al, 1997;Thompson et al, 1998;Prichett et al, 2000;Justesen et al, 2001;Abdallah et al, 2004;Nuttall and Gimble, 2004], based on the lineagespecific marker expression. Mesenchymal progenitor cells cultured from explants of adult trabecular bone serve as an excellent system to investigate the biology of normal human bone cells.…”

Decreased Expression of the Human Urea Transporter SLC14A1 in Bone is Induced by Cytokines and Stimulates Adipogenesis of Mesenchymal Progenitor Cells

“…Primary human trabecular osteoblast precursors express human solute carrier family 14 (urea transporter), member 1 (SLC14A1, also called HUT11 or UT-B; GenBank ID: AF263545) [15,16]. The functional protein is found in the cell membrane and enables the directed flow of urea across the membrane [15,17].…”