The function of adipocytes in the bone marrow stroma: an update.

The adipocyte is the most abundant stromal cell phenotype in adult human bone marrow. Four hypotheses may explain their function. First, adipocytes may serve a passive role, simply occupying excess space in the bone marrow cavity. Second, they may play an active role in systemic lipid metabolism. Third, adipocytes may provide a localized energy reservoir in the bone marrow. Or fourth, marrow adipocytes may contribute directly to the promotion of hematopoiesis and influence osteogenesis. This article reviews recent findings concerning bone marrow adipocyte morphology and physiology, the transcriptional and cytokine mechanisms regulating their differentiation, and the interrelationships existing between bone marrow adipocytes, hematopoiesis, and osteogenesis. Overall, these data lend support to a "plastic" model of bone marrow stromal cell differentiation; adipocytes may share common functions with stromal stem cells, osteoblasts, and hematopoietic supportive cells.

[1]  B. Shenker,et al.  Induction of rapid osteoblast differentiation in rat bone marrow stromal cell cultures by dexamethasone and BMP-2. , 1994, Developmental biology.

[2]  S. Asano,et al.  Adhesion of NFS-60 myeloid leukemia cells to MC3T3-G2/PA6 stromal cells induces granulocyte colony-stimulating factor production , 1994 .

[3]  S. Wientroub,et al.  Marrow adipocytes regulate growth and differentiation of osteoblasts. , 1993, Biochemical and biophysical research communications.

[4]  T. Martin,et al.  Modulation of osteoclast differentiation. , 1992, Endocrine reviews.

[5]  P Meunier,et al.  Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies. , 1971, Clinical orthopaedics and related research.

[6]  O. MacDougald,et al.  Transcriptional regulation of gene expression during adipocyte differentiation. , 1995, Annual review of biochemistry.

[7]  Y. Shimizu,et al.  T lymphocyte adhesion molecules. , 1989, The Year in immunology.

[8]  B. Spiegelman,et al.  Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor , 1994, Cell.

[9]  J. Gimble The function of adipocytes in the bone marrow stroma. , 1990, The New biologist.

[10]  A. Boyde,et al.  Marrow stromal (Western-Bainton) cells: identification, morphometry, confocal imaging and changes in disease. , 1993, Bone.

[11]  J. Gimble,et al.  Cloning and characterization of the murine activin receptor like kinase-1 (ALK-1) homolog. , 1995, Biochemical and biophysical research communications.

[12]  G. Yancopoulos,et al.  Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal/osteoblastic cells. , 1996, The Journal of clinical investigation.

[13]  J. Gimble,et al.  Regulation of bone marrow stromal cell differentiation by cytokines whose receptors share the gp130 Protein , 1994, Journal of cellular biochemistry.

[14]  M. Obinata,et al.  Establishment and characterization of bone marrow stromal cell lines that support osteoclastogenesis. , 1995, Endocrinology.

[15]  S. Beck,et al.  Tenascin is a cytoadhesive extracellular matrix component of the human hematopoietic microenvironment , 1993, The Journal of cell biology.

[16]  J. Gimble,et al.  Adipogenesis in a murine bone marrow stromal cell line capable of supporting B lineage lymphocyte growth and proliferation: Biochemical and molecular characterization , 1990, European journal of immunology.

[17]  J. Gimble,et al.  Analysis of the native murine bone morphogenetic protein serine threonine kinase type I receptor (ALK‐3) , 1996, Journal of cellular physiology.

[18]  R. Fässler,et al.  Downregulation of tenascin expression by glucocorticoids in bone marrow stromal cells and in fibroblasts , 1993, The Journal of cell biology.

[19]  A. Peled,et al.  Interactions between leukemia cells and bone marrow stromal cells: stroma-supported growth vs. serum dependence and the roles of TGF-beta and M-CSF. , 1996, Experimental hematology.

[20]  A. Caplan,et al.  Differentiation potential of conditionally immortalized mesenchymal progenitor cells from adult marrow of a H‐2Kb‐tsA58 transgenic mouse , 1996, Journal of cellular physiology.

[21]  N. Takahashi,et al.  1α,25‐Dihydroxyvitamin D3 modulation in lipid metabolism in established bone marrow‐derived stromal cells, MC3T3‐G2/PA6 , 1992, Journal of cellular biochemistry.

[22]  P. Carlsson,et al.  Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending. , 1994, The EMBO journal.

[23]  J. Canick,et al.  Human fatty marrow aromatizes androgen to estrogen. , 1980, The Journal of clinical endocrinology and metabolism.

[24]  T. Ikeda,et al.  1 alpha,25-dihydroxyvitamin D3 regulates in vivo production of the third component of complement (C3) in bone. , 1992, Endocrinology.

[25]  B. Spiegelman,et al.  mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. , 1994, Genes & development.

[26]  L. Weiss,et al.  Seasonal variations in hematopoiesis in the dermal bones of the nine‐banded armadillo , 1956, The Anatomical record.

[27]  T. Martin,et al.  The bone marrow-derived stromal cell lines MC3T3-G2/PA6 and ST2 support osteoclast-like cell differentiation in cocultures with mouse spleen cells. , 1989, Endocrinology.

[28]  L. Weiss,et al.  Adipocyte development and the loss of erythropoietic capacity in the bone marrow of mice after sustained hypertransfusion. , 1982, Blood.

[29]  Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. , 1992, Molecular endocrinology.

[30]  R. Derynck,et al.  Modulation of expression and cell surface binding of members of the transforming growth factor-beta superfamily during retinoic acid-induced osteoblastic differentiation of multipotential mesenchymal cells. , 1993, Molecular endocrinology.

[31]  A. Admon,et al.  SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene , 1993, Cell.

[32]  P. Witte,et al.  Enrichment of primary lymphocyte‐supporting stromal cells and characterization of associated B lymphocyte progenitors , 1992, European journal of immunology.

[33]  J. Triffitt,et al.  Human bone tissue formation in diffusion chamber culture in vivo by bone-derived cells and marrow stromal fibroblastic cells. , 1995, Bone.

[34]  G S Stein,et al.  Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. , 1993, Endocrine reviews.

[35]  R. Jilka,et al.  Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. , 1995, The New England journal of medicine.

[36]  I. Asahina,et al.  Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells. , 1996, Experimental cell research.

[37]  J. Gimble,et al.  Osteoblastic gene expression during adipogenesis in hematopoietic supporting murine bone marrow stromal cells , 1993, Journal of cellular physiology.

[38]  J. Gimble,et al.  Response of bone marrow stromal cells to adipogenic antagonists , 1989, Molecular and cellular biology.

[39]  X. Chen,et al.  Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promoter use and different splicing yield two mPPAR gamma isoforms. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[40]  C. Strader,et al.  Isolation of a preadipocyte cell line from rat bone marrow and differentiation to adipocytes. , 1995, Endocrinology.

[41]  M. Glimcher,et al.  Receptor-Ligand Interaction Between CD44 and Osteopontin (Eta-1) , 1996, Science.

[42]  M. Mielcarek,et al.  CD14+ cells in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells induce secretion of interleukin-6 and G-CSF by marrow stroma. , 1996, Blood.

[43]  Mayumi Sato,et al.  Demonstration of 1α,25‐dihydroxyvitamin D3 receptor‐like molecule in ST 13 and 3T3 L1 preadipocytes and its inhibitory effects on preadipocyte differentiation , 1988 .

[44]  A. Parfitt,et al.  Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence. , 1996, The Journal of clinical investigation.

[45]  G. Passeri,et al.  Interleukin-11: a new cytokine critical for osteoclast development. , 1994, The Journal of clinical investigation.

[46]  L Berga,et al.  Age-related variations of fat tissue fraction in normal human bone marrow depend both on size and number of adipocytes: a stereological study. , 1989, Experimental hematology.

[47]  H. Broxmeyer,et al.  Increased osteoclast development after estrogen loss: mediation by interleukin-6 , 1992 .

[48]  J. Aubin,et al.  1,25-dihydroxyvitamin D3 stimulates adipocyte differentiation in cultures of fetal rat calvaria cells: comparison with the effects of dexamethasone. , 1994, Endocrinology.

[49]  J. Gimble,et al.  Bone morphogenetic proteins inhibit adipocyte differentiation by bone marrow stromal cells , 1995, Journal of cellular biochemistry.

[50]  J. Lehmann,et al.  A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation , 1995, Cell.

[51]  K. Segawa,et al.  Multipotent marrow stromal cell line is able to induce hematopoiesis in vivo , 1992, Journal of cellular physiology.

[52]  J. Aubin,et al.  Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: effect of dexamethasone , 1988, The Journal of cell biology.

[53]  L. Frantsve,et al.  Cytokine production and heterogeneity of primary stromal cells that support B lymphopoiesis , 1993, European journal of immunology.

[54]  T. Møller-Pedersen,et al.  Effects of in vivo estrogen treatment on adipose tissue metabolism and nuclear estrogen receptor binding in isolated rat adipocytes , 1992, Molecular and Cellular Endocrinology.

[55]  T. Kinoshita,et al.  The biological roles of the third component of complement in osteoclast formation. , 1993, Endocrinology.

[56]  J. Greenberger,et al.  Adipogenesis in a myeloid supporting bone marrow stromal cell line , 1992, Journal of cellular biochemistry.

[57]  B. Thomson,et al.  Preliminary characterization of porcine bone marrow stromal cells: Skeletogenic potential, colony‐forming activity, and response to dexamethasone, transforming growth factor β, and basic fibroblast growth factor , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[58]  C. Devlin,et al.  The effects of dexamethasone and 1,25-dihydroxyvitamin D3 on osteogenic differentiation of human marrow stromal cells in vitro. , 1994, Archives of oral biology.

[59]  A. Caplan,et al.  Cell surface antigens on human marrow-derived mesenchymal cells are detected by monoclonal antibodies. , 1992, Bone.

[60]  J. Lehmann,et al.  Peroxisome proliferator-activated receptor-gamma activation by thiazolidinediones induces adipogenesis in bone marrow stromal cells. , 1996, Molecular pharmacology.

[61]  J. Triffitt,et al.  Adipocytic cells cultured from marrow have osteogenic potential. , 1991, Journal of cell science.

[62]  B. Riggs,et al.  Isolation and characterization of osteoblast precursor cells from human bone marrow , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[63]  N. Wolf,et al.  An age-related reduction in the replicative capacity of two murine hematopoietic stroma cell types. , 1992, Experimental hematology.

[64]  M. Owen Marrow stromal stem cells , 1988, Journal of Cell Science.

[65]  M. Tavassoli Fatty Involution of Marrow and the Role of Adipose Tissue in Hemopoiesis , 1989 .

[66]  S. Manolagas Bone marrow, cytokines, and bone remodeling , 1995 .

[67]  I. Kawashima,et al.  Molecular cloning of cDNA encoding adipogenesis inhibitory factor and identity with interleukin‐11 , 1991, FEBS letters.

[68]  Y. Ishimi,et al.  Transcriptional regulation of the production of the third component of complement (C3) by 1 alpha,25-dihydroxyvitamin D3 in mouse marrow-derived stromal cells (ST2) and primary osteoblastic cells. , 1991, Endocrinology.

[69]  K. Tachibana,et al.  Colony-stimulating factor 1 expression is down-regulated during the adipocyte differentiation of H-1/A marrow stromal cells and induced by cachectin/tumor necrosis factor , 1991, Molecular and cellular biology.

[70]  R. Martin,et al.  Relationships between marrow fat and bone turnover in ovariectomized and intact rats. , 1991, Bone.

[71]  P. Kincade Cell interaction molecules and cytokines which participate in B lymphopoiesis. , 1992, Bailliere's clinical haematology.

[72]  M. Tavassoli,et al.  Bone Marrow Histogenesis: A Comparison of Fatty and Red Marrow , 1970, Science.

[73]  S. Graves,et al.  Formation of mineralized nodules by bone derived cells in vitro: a model of bone formation? , 1993, American journal of medical genetics.

[74]  M. Katoh,et al.  Induction of bone resorbing-activity by mouse stromal cell line, MC3T3-G2/PA6. , 1995, Bone.

[75]  J. Triffitt,et al.  In vitro effects of growth factors and dexamethasone on rat marrow stromal cells. , 1995, Clinical orthopaedics and related research.

[76]  M. Noble,et al.  Generation of osteoclast-inductive and osteoclastogenic cell lines from the H-2KbtsA58 transgenic mouse. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[77]  H. Sul,et al.  Control of adipocyte differentiation. , 1995, The Biochemical journal.

[78]  C. Devlin,et al.  Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. , 1992, Journal of cell science.

[79]  A. Rahmouni,et al.  Normal age-related patterns of cellular and fatty bone marrow distribution in the axial skeleton: MR imaging study. , 1990, Radiology.

[80]  S. Niida,et al.  BriefDefinitive Report Essential Role of Macrophage Colony-Stimulating Factor in the Osteoclast Differentiation Supported by , 2022 .

[81]  D. Benayahu,et al.  Myeloblastic cell line expresses osteoclastic properties following coculture with marrow stromal adipocytes , 1994, Journal of cellular biochemistry.

[82]  E. Deryugina,et al.  Stromal cells in long-term cultures: keys to the elucidation of hematopoietic development? , 1993, Critical reviews in immunology.

[83]  C. Devlin,et al.  Dexamethasone induction of osteoblast mRNAs in rat marrow stromal cell cultures , 1991, Journal of cellular physiology.

[84]  S. Delikat,et al.  IL-1 beta inhibits adipocyte formation in human long-term bone marrow culture. , 1993, Experimental hematology.

[85]  P. Grimaldi,et al.  Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36. , 1993, The Journal of biological chemistry.

[86]  B. Ratnikov,et al.  Clonal analysis of primary marrow stroma: functional homogeneity in support of lymphoid and myeloid cell lines and identification of positive and negative regulators. , 1994, Experimental hematology.

[87]  L. Kearney,et al.  Effects of human marrow stromal cells on proliferation by human granulocytic (GM‐CFC), erythroid (BFU‐E) and mixed (Mix‐CFC) colony‐forming cells , 1983, British journal of haematology.

[88]  A I Caplan,et al.  The mesengenic process. , 1994, Clinics in plastic surgery.

[89]  J. Falkenburg,et al.  Regulation of myelopoiesis by murine fibroblastic and adipogenic cell lines. , 1993, Experimental hematology.

[90]  G. Balian,et al.  Two cell lines from bone marrow that differ in terms of collagen synthesis, osteogenic characteristics, and matrix mineralization. , 1993, The Journal of bone and joint surgery. American volume.

[91]  L. Weiss,et al.  The hematopoietic stroma. , 1984, The American journal of anatomy.

[92]  H. Snoeck,et al.  Characterization and purification of osteogenic cells from murine bone marrow by two-color cell sorting using anti-Sca-1 monoclonal antibody and wheat germ agglutinin , 1994 .

[93]  T. Martin,et al.  The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures , 1996, The Journal of experimental medicine.