Bone morphogenetic proteins inhibit adipocyte differentiation by bone marrow stromal cells

Abstract

The bone morphogenetic proteins were originally identified based on their ability to induce ectopic bone formation in vivo and have since been identified as members of the transforming growth factor-beta gene superfamily. It has been well established that the bone morphogenetic cytokines enhance osteogenic activity in bone marrow stromal cells in vitro. Recent reports have described how bone morphogenetic proteins inhibited myogenic differentiation of bone marrow stromal cells in vitro. In vivo, bone marrow stromal cells differentiate along the related adipogenic pathway with advancing age. The current work reports the inhibitory effects of the bone morphorphogenetic proteins on adipogenesis in a multipotent murine bone marrow stromal cell line, BMS2. When exposed to bone morphogenetic protein-2, the pre-adipocyte BMS2 cells exhibited the expected induction of the osteogenic-related enzyme, alkaline phosphatase. Following induction of the BMS2 cells with adipogenic agonists, adipocyte differentiation was assessed by morphologic, enzymatic, and mRNA markers. Flow cytometric analysis combined with staining by the lipophilic fluorescent dye, Nile red, was used to quantitate the extent of lipid accumulation within the BMS2 cells. By this morphologic criteria, the bone morphogenetic proteins inhibited adipogenesis at concentrations of 50 to 500 ng/ml. This correlated with decreased levels of adipocyte specific enzymes and mRNAs. The BMS2 pre-adipocytes constitutively expressed mRNA encoding bone morphogenetic protein-4 and this was inhibited by adipogenic agonists. Together, these findings demonstrate that bone morphogenetic proteins act as adipogenic antagonists. This supports the hypothesis that adipogenesis and osteogenesis in the bone marrow microenvironment are reciprocally regulated.

Effect of Bone Morphogenetic Protein-2 (BMP-2) or Troglitazone, as an Inducer of Osteogenic Cells or Adipocytes, on Differentiation of a Bone Marrow Mesenchymal Progenitor Cell Line Established from Temperature-Sensitive (ts) Simian Virus (SV) 40 T-Antigen Gene Transgenic Mice

“…This supports the hypothesis that there are close relationships between osteogenic cell differentiation and adipocyte differentiation and that they are reciprocally regulated. [52][53][54] It is of great interest to examine the mechanism of commitment to each phenotype using TBR31-2 with consideration of the effects of BMP-2 and troglitazone.…”

Reduced Expression of Interleukin-11 in Bone Marrow Stromal Cells of Senescence-Accelerated Mice (SAMP6): Relationship to Osteopenia with Enhanced Adipogenesis

“…(26) In contrast, bone morphogenetic proteins are potent stimulators of osteoblastic differentiation and have been shown to inhibit adipocytic differentiation of bone marrow stromal cells. (27) Thus, adipogenesis and osteoblastogenesis appears to be reciprocally regulated in the bone marrow. (11) Osteotropic factors, such as PTH, PTH-related proteins, (22) and IL-1, (21) are shown to stimulate IL-11 expression in bone marrow cells and osteoblasts.…”

Establishment of an adherent cell layer from human umbilical cord blood

“…This finding differs from that reported by Ye et al (1994), although the reasons for this discrepancy are unclear. Although, with advancing age, marrow stromal cells can differentiate along an adipogenesis pathway, the exact function of these cells is still not clear (Gimble et al, 1995).…”