Adipogenesis in a myeloid supporting bone marrow stromal cell line

Abstract

The bone marrow stroma contains pre-adipocyte cells which are part of the hemopoietic microenvironment. Cloned stromal cell lines differ both in their ability to support myeloid and lymphoid development and in their ability to undergo adipocyte differentiation in vitro. These processes have been examined in the +/+2.4 murine stromal cell line and compared to other stromal and pre-adipocyte cell lines. In long term cultures, the +/+2.4 stromal cells support myeloid cell growth, consistent with their expression of macrophage-colony stimulating factor mRNA. However, despite the presence of mRNA for the lymphoid supportive cytokines interleukins 6 and 7, +/+2.4 cells failed to support stromal cell dependent B lineage lymphoid cells in vitro, suggesting that these stromal cells exhibit only a myelopoietic support function. The +/+2.4 cells differentiate into adipocyte spontaneously when cultured in 10% fetal bovine serum. The process of adipogenesis can be accelerated by a number of a agonists based on morphologic and gene maker criteria. Following induction with hydrocortisone, methylisobutylxanthine, indomethacin, and insulin in combination a time dependent increase in the steady state mRNA and enzymes activity levels of the following adipocyte specific genes was observed: adipocyte P2, adipsin, CAAT/enhancer binding protein, and lipoprotein lipase. In contrast, adipogenesis were accompanied by a slight decrease in the signal intensity of the macrophage-colony stimulating factor mRNA level, similar to that which has been reported in other bone marrow stromal cell lines. These data demonstrate that although the lympho-hematopoietic support fuction of pre-adipocyte bone marrow stormal cell lines is heterogeneous, they share a common mechanism of adipognensis.