Response of bone marrow stromal cells to adipogenic antagonists.

Gimble, J. M.; Dorheim, M A; Cheng, Qi; Pekala, Phillip H.; Enerbäck, Sven; Ellingsworth, Larry; Kincade, Paul W.; Wang, C.-S.

doi:10.1128/mcb.9.11.4587

Cited by 45 publications

(19 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro, adipocyte differentiation by stromal cells is accompanied by a loss of gene markers consistent with an osteoblast-like phenotype, including osteocalcin, type I and type I11 collagen, and osteopontin [Beresford et al, 1992; Dorheim et al, 19931. It has been suggested that osteogenic inductive cytokines may act as negative regulators of adipogenesis [Bennett et al, 1991; Beresford et al, 19921.The current work tests this hypothesis using the BMSB cell line as a multi-potent bone marrow stromal cell model [Pietrangeli et al, 1988;Gimble et al, 1989 Dorheim et al, 19931. These cells support lympho-hematopoiesis, undergo adipocyte differentiation, and constitutively display gene markers consistent with an osteoblast phenotype.…”

mentioning

confidence: 63%

Bone morphogenetic proteins inhibit adipocyte differentiation by bone marrow stromal cells

Gimble

Morgan

Kelly

et al. 1995

J of Cellular Biochemistry

173

104

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 63%

Bone morphogenetic proteins inhibit adipocyte differentiation by bone marrow stromal cells

Gimble

Morgan

Kelly

et al. 1995

J of Cellular Biochemistry

173

104

View full text Add to dashboard Cite

show abstract

“…Earlier studies had associated BM adipocytes with increased M@-CSF and granulocyte-M@-CSF production based on biological assays [12,68]. BMM adipocytes also retained the ability to markedly increase their steady-state level of IL 6 mRNA in response to the cytokines IL1, TGF-P and TNE Each of these cytokines (IL1, TGF-P, TNF) has been to act as an adipogenic antagonist on BMS2 cells (Gimble et al, in press) [62,[69][70][71][72][73][74]. This suggests that the differentiation state* and functional activity of stromal cells can be regulated by factors released locally in the BM microenvironment in addition to more classical endocrine hormones.…”

Section: Discussionmentioning

confidence: 97%

Adipogenesis in a murine bone marrow stromal cell line capable of supporting B lineage lymphocyte growth and proliferation: Biochemical and molecular characterization

et al. 1990

View full text Add to dashboard Cite

Recent advances in long-term bone marrow (BM) culture techniques have allowed investigators to dissect cellular components responsible for lympho hematopoiesis. Consequently, a number of "stromal" cell clones have been developed which are capable of supporting B lineage lymphocyte growth and proliferation in vitro by direct cell-cell interactions and the release of cytokines. While much work has focused on the support function of these cells, questions remain regarding their own differentiation potential. We have examined adipogenesis in the cloned BM stromal cell, BMS2. The presence of hydrocortisone, methylisobutylxanthine, or 30% fetal calf serum each accelerated adipocyte differentiation. This process was accompanied by the accumulation of triglycerides and cholesterol esters along with the induction of adipocyte-specific enzymes. Likewise, the steady-state level of mRNA transcripts increased for genes related to lipid metabolism. However, the pattern of mRNA expression in BMS2 adipocytes differed from that of a well-established, pre-adipocyte cell line, 3T3-L1, with respect to the following genes: glycerol phosphate dehydrogenase, CAAT/enhancer binding protein and angiotensinogen. Adipocyte BMS2 cells retailed the ability to support stromal cell-dependent B lineage lymphocytes in methylcellulose assays. The adipocytes continued to express macrophage-colony-stimulating factor mRNA constitutively and interleukin 6 mRNA in an inducible manner, similar to the BMS2 pre-adipocytes. Together, these data document a close developmental relationship between a specialized fibroblasts and adipocytes in the BM and suggest that adipocyte stromal cells may play an active role in lympho-hematopoiesis.

show abstract

“…These lines have been derived either directly from adipose tissue or from fetal fibroblasts [Ailhaud, 19821. Although many bone marrow pre-adipocyte stromal cell lines have been cloned, studies examining their adipocyte differentiation at the molecular level are limited [Gimble et al, 1989[Gimble et al, , 1990Gimble, 1990;Grigoriadis et al, 1990;Watanabe and Takano, 19911. In the lymphopoietic-supporting BMS2 stromal cell line, adipogenesis correlated with the induction of aP2, adipsin, and LPL steady state mRNA levels as well as increased enzyme activity for glycerophosphate dehydrogenase (GPD) and LPL [Gimble et al, 19901.…”

Section: Discussionmentioning

confidence: 99%

“…Northern blots were prepared with 10-20 mcg of total RNA per lane according to the method of Thomas [Gimble et al, 1989;Thomas, 19801.…”

Section: Rna Purification and Northern Blot Analysismentioning

confidence: 99%

Adipogenesis in a myeloid supporting bone marrow stromal cell line

Gimble

Youkhana

Hua

et al. 1992

J of Cellular Biochemistry

View full text Add to dashboard Cite

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 adipocytes spontaneously when cultured in 10% fetal bovine serum. The process of adipogenesis can be accelerated by a number of agonists based on morphologic and gene marker criteria. Following induction with hydrocortisone, methylisobutylxanthine, indomethacin, and insulin in combination, a time dependent increase in the steady state mRNA and enzyme activity levels of the following adipocyte specific genes was observed: adipocyte P2, adipsin, CAAT/enhancer binding protein, and lipoprotein lipase. In contrast, adipogenesis was 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 function of pre-adipocyte bone marrow stromal cell lines is heterogeneous, they share a common mechanism of adipogenesis.

show abstract

Response of bone marrow stromal cells to adipogenic antagonists.

Cited by 45 publications

References 62 publications

Bone morphogenetic proteins inhibit adipocyte differentiation by bone marrow stromal cells

Bone morphogenetic proteins inhibit adipocyte differentiation by bone marrow stromal cells

Adipogenesis in a murine bone marrow stromal cell line capable of supporting B lineage lymphocyte growth and proliferation: Biochemical and molecular characterization

Adipogenesis in a myeloid supporting bone marrow stromal cell line

Contact Info

Product

Resources

About