Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Calcified Tissue International
Published in: Calcified Tissue International 1/2014

01-01-2014 | Review

Adipocytes and the Regulation of Bone Remodeling: A Balancing Act

Authors: Mark E. Nuttall, Forum Shah, Vikramjeet Singh, Caasy Thomas-Porch, Trivia Frazier, Jeffrey M. Gimble

Published in: Calcified Tissue International | Issue 1/2014

Login to get access

Abstract

Throughout life, a balance exists within the marrow cavity between adipose tissue and bone. Each tissue derives from a common progenitor cell known both as a “bone marrow-derived multipotent stromal cell” and as a “mesenchymal stem cell” (BMSC). The majority of in vitro and in vivo data suggest that BMSCs differentiate into adipocytes or osteoblasts in a reciprocal manner. For example, while ligand induction of the transcription factors peroxisome proliferator-activated receptor γ initiates BMSC adipogenesis, it suppresses osteogenesis. Nevertheless, this hypothesis may oversimplify a complex regulatory paradigm. The picture may be further complicated by the systemic impact of extramedullary adipose depots on bone via the secretion of protein adipokines and lipid metabolites. This review focuses on past and current literature examining the mechanisms governing the adipose–bone interface.
Literature
1.
Beresford JN, Bennett JH, Devlin C et al (1992) Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J Cell Sci 102:341–351PubMed
2.
Gimble JM, Robinson CE, Wu X et al (1996) The function of adipocytes in the bone marrow stroma: an update. Bone 19:421–428PubMedCrossRef
3.
4.
Nuttall ME, Gimble JM (2004) Controlling the balance between osteoblastogenesis and adipogenesis and the consequent therapeutic implications. Curr Opin Pharmacol 4:290–294PubMedCrossRef
5.
6.
Friedenstein AJ, Piatetzky S II, Petrakova KV (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16:381–390PubMed
7.
Friedenstein AY (1968) Induction of bone tissue by transitional epithelium. Clin Orthop Relat Res 59:21–37PubMedCrossRef
8.
Friedenstein AJ (1976) Precursor cells of mechanocytes. Int Rev Cytol 47:327–359PubMed
9.
Owen M, Friedenstein AJ (1988) Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found Symp 136:42–60PubMed
10.
Weisberg SP, McCann D, Desai M et al (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808PubMedCentralPubMed
11.
Xu H, Barnes GT, Yang Q et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830PubMedCentralPubMed
12.
Strissel KJ, Stancheva Z, Miyoshi H et al (2007) Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56:2910–2918PubMedCrossRef
13.
Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359PubMedCrossRef
14.
15.
Seale P, Conroe HM, Estall J et al (2011) Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest 121:96–105PubMedCentralPubMedCrossRef
16.
17.
Wu J, Bostrom P, Sparks LM et al (2010) Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366–376CrossRef
18.
Huggins C, Blocksom BH, Noonan WJ (1936) Temperature conditions in bone marrow of rabbit, pigeon, and albino rat. Am J Physiol 115:395–401
19.
Huggins C, Noonan WJ (1936) An increase in reticulo-endothelial cells in outlying bone marrow consequent upon a local increase in temperature. J Exp Med 64:275–280PubMedCentralPubMedCrossRef
20.
Krings A, Rahman S, Huang S et al (2012) Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes. Bone 50:546–552PubMedCentralPubMedCrossRef
21.
Salisbury E, Hipp J, Olmsted-Davis EA et al (2012) Histologic identification of brown adipose and peripheral nerve involvement in human atherosclerotic vessels. Hum Pathol 43:2212–2223CrossRef
22.
Olmsted-Davis E, Gannon FH, Ozen M et al (2007) Hypoxic adipocytes pattern early heterotopic bone formation. Am J Pathol 170:620–632PubMedCrossRef
23.
Nishio N, Yoneshiro T, Nakahara M et al (2012) Production of functional classical brown adipocytes from human pluripotent stem cells using hemopoietin cocktail without gene transfer. Cell Metab 16:394–406PubMedCrossRef
24.
Taichman RS, Emerson SG (1994) Human osteoblasts support hematopoiesis through the production of granulocyte colony-stimulating factor. J Exp Med 179:1677–1682PubMedCrossRef
25.
Zhu J, Garrett R, Jung Y et al (2007) Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cells. Blood 109:3706–3712PubMedCrossRef
26.
Zhang J, Niu C, Ye L et al (2003) Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425:836–841PubMedCrossRef
27.
Calvi LM, Adams GB, Weibrecht KW et al (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–846PubMedCrossRef
28.
Gimble JM (1990) The function of adipocytes in the bone marrow stroma. New Biol 2:304–312PubMed
29.
Yokota T, Meka CS, Medina KL et al (2002) Paracrine regulation of fat cell formation in bone marrow cultures via adiponectin and prostaglandins. J Clin Invest 109:1303–1310PubMedCentralPubMed
30.
Yokota T, Meka CS, Kouro T et al (2003) Adiponectin, a fat cell product, influences the earliest lymphocyte precursors in bone marrow cultures by activation of the cyclooxygenase–prostaglandin pathway in stromal cells. J Immunol 171:5091–5099PubMed
31.
32.
Cousin B, Andre M, Arnaud E et al (2003) Reconstitution of lethally irradiated mice by cells isolated from adipose tissue. Biochem Biophys Res Commun 301:1016–1022PubMedCrossRef
33.
Han J, Koh YJ, Moon HR et al (2010) Adipose tissue is an extramedullary reservoir for functional hematopoietic stem and progenitor cells. Blood 115:957–964PubMedCrossRef
34.
Corre J, Barreau C, Cousin B et al (2006) Human subcutaneous adipose cells support complete differentiation but not self-renewal of hematopoietic progenitors. J Cell Physiol 208:282–288PubMedCrossRef
35.
Kilroy GE, Foster S, Wu X et al (2007) Cytokine profile of human adipose-derived stem cells: expression of angiogenic, hematopoietic, and pro-inflammatory factors. J Cell Physiol 212:702–709PubMedCrossRef
36.
Kletzien RF, Clarke SD, Ulrich RG (1992) Enhancement of adipocyte differentiation by an insulin-sensitizing agent. Mol Pharmacol 41:393–398PubMed
37.
Kletzien RF, Foellmi LA, Harris PK et al (1992) Adipocyte fatty acid-binding protein: regulation of gene expression in vivo and in vitro by an insulin-sensitizing agent. Mol Pharmacol 42:558–562PubMed
38.
Tontonoz P, Hu E, Graves RA et al (1994) mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 8:1224–1234PubMedCrossRef
39.
Gimble JM, Robinson CE, Wu X et al (1996) Peroxisome proliferator–activated receptor-gamma activation by thiazolidinediones induces adipogenesis in bone marrow stromal cells. Mol Pharmacol 50:1087–1094PubMed
40.
Lecka-Czernik B, Gubrij I, Moerman EJ et al (1999) Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPARgamma2. J Cell Biochem 74:357–371PubMedCrossRef
41.
42.
43.
Tornvig L, Mosekilde LI, Justesen J et al (2001) Troglitazone treatment increases bone marrow adipose tissue volume but does not affect trabecular bone volume in mice. Calcif Tissue Int 69:46–50PubMedCrossRef
44.
Lazarenko OP, Rzonca SO, Hogue WR et al (2007) Rosiglitazone induces decreases in bone mass and strength that are reminiscent of aged bone. Endocrinology 148:2669–2680PubMedCentralPubMedCrossRef
45.
Akune T, Ohba S, Kamekura S et al (2004) PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest 113:846–855PubMedCentralPubMed
46.
Kawaguchi H, Akune T, Yamaguchi M et al (2005) Distinct effects of PPARgamma insufficiency on bone marrow cells, osteoblasts, and osteoclastic cells. J Bone Miner Metab 23:275–279PubMedCrossRef
47.
Ali AA, Weinstein RS, Stewart SA et al (2005) Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation. Endocrinology 146:1226–1235PubMedCrossRef
48.
Sottile V, Seuwen K, Kneissel M (2004) Enhanced marrow adipogenesis and bone resorption in estrogen-deprived rats treated with the PPARgamma agonist BRL49653 (rosiglitazone). Calcif Tissue Int 75:329–337PubMedCrossRef
49.
Chan BY, Gartland A, Wilson PJ et al (2007) PPAR agonists modulate human osteoclast formation and activity in vitro. Bone 40:149–159PubMedCrossRef
50.
Hassumi MY, Silva-Filho VJ, Campos-Júnior JC et al (2009) PPAR-gamma agonist rosiglitazone prevents inflammatory periodontal bone loss by inhibiting osteoclastogenesis. Int Immunopharmacol 9:1150–1158PubMedCrossRef
51.
Wei W, Wang X, Yang M et al (2010) PGC1beta mediates PPARgamma activation of osteoclastogenesis and rosiglitazone-induced bone loss. Cell Metab 11:503–516PubMedCentralPubMedCrossRef
52.
Schwartz AV, Sellmeyer DE, Vittinghoff E et al (2006) Thiazolidinedione (TZD) use and bone loss in older diabetic adults. J Clin Endocrinol Metab 91:3349–3354PubMedCentralPubMedCrossRef
53.
54.
Tanne JH (2007) FDA places “black box” warning on antidiabetes drugs. Br Med J 334:1237CrossRef
55.
Nissen SE, Wolski K (2007) Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 356:2457–2471PubMedCrossRef
56.
Umek RM, Friedman AD, McKnight SL (1991) CCAAT-enhancer binding protein: a component of a differentiation switch. Science 251:288–292PubMedCrossRef
57.
Yeh WC, Cao Z, Classon M et al (1995) Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev 9:168–181PubMedCrossRef
58.
Cao Z, Umek RM, McKnight SL (1991) Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev 5:1538–1552PubMedCrossRef
59.
Schopfer FJ, Lin Y, Baker PR et al (2005) Nitrolinoleic acid: an endogenous peroxisome proliferator–activated receptor gamma ligand. Proc Natl Acad Sci USA 102:2340–2345PubMedCrossRef
60.
Li X, Jin L, Cui Q et al (2005) Steroid effects on osteogenesis through mesenchymal cell gene expression. Osteoporos Int 16:101–108PubMedCrossRef
61.
Wang GJ, Cui Q, Balian G (2000) The Nicolas Andry award. The pathogenesis and prevention of steroid-induced osteonecrosis. Clin Orthop Relat Res 370:295–310PubMedCrossRef
62.
Weinstein RS, Jilka RL, Parfitt AM et al (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102:274–282PubMedCentralPubMedCrossRef
63.
64.
Kha HT, Basseri B, Shouhed D et al (2004) Oxysterols regulate differentiation of mesenchymal stem cells: pro-bone and anti-fat. J Bone Miner Res 19:830–840PubMedCrossRef
65.
Kim WK, Meliton V, Tetradis S et al (2010) Osteogenic oxysterol, 20(S)-hydroxycholesterol, induces notch target gene expression in bone marrow stromal cells. J Bone Miner Res 25:782–795PubMedCrossRef
66.
Amantea CM, Kim WK, Meliton V et al (2008) Oxysterol-induced osteogenic differentiation of marrow stromal cells is regulated by Dkk-1 inhibitable and PI3-kinase mediated signaling. J Cell Biochem 105:424–436PubMedCentralPubMedCrossRef
67.
Richardson JA, Amantea CM, Kianmahd B et al (2007) Oxysterol-induced osteoblastic differentiation of pluripotent mesenchymal cells is mediated through a PKC- and PKA-dependent pathway. J Cell Biochem 100(5):1131–1145PubMedCrossRef
68.
Martin RB, Chow BD, Lucas PA (1990) Bone marrow fat content in relation to bone remodeling and serum chemistry in intact and ovariectomized dogs. Calcif Tissue Int 46:189–194PubMedCrossRef
69.
Martin RB, Zissimos SL (1991) Relationships between marrow fat and bone turnover in ovariectomized and intact rats. Bone 12:123–131PubMedCrossRef
70.
Schoutens A, Verhas M, L’Hermite-Baleriaux M et al (1984) Growth and bone haemodynamic responses to castration in male rats. Reversibility by testosterone. Acta Endocrinol (Copenh) 107:428–432
71.
Johnson AL, Rendano VT (1984) Effects of castration, with and without testosterone replacement, on leg bone integrity in the domestic fowl. Am J Vet Res 45:319–325PubMed
72.
Benvenuti S, Cellai I, Luciani P et al (2011) Androgens and estrogens prevent rosiglitazone-induced adipogenesis in human mesenchymal stem cells. J Endocrinol Invest 35:365–371PubMed
73.
Dang ZC, van Bezooijen RL, Karperien M et al (2002) Exposure of KS483 cells to estrogen enhances osteogenesis and inhibits adipogenesis. J Bone Miner Res 17:394–405PubMedCrossRef
74.
Heim M, Frank O, Kampmann G et al (2004) The phytoestrogen genistein enhances osteogenesis and represses adipogenic differentiation of human primary bone marrow stromal cells. Endocrinology 145:848–859PubMedCrossRef
75.
Okazaki R, Inoue D, Shibata M et al (2002) Estrogen promotes early osteoblast differentiation and inhibits adipocyte differentiation in mouse bone marrow stromal cell lines that express estrogen receptor (ER) alpha or beta. Endocrinology 143:2349–2356PubMed
76.
Duque G, Macoritto M, Kremer R (2004) Vitamin D treatment of senescence accelerated mice (SAM-P/6) induces several regulators of stromal cell plasticity. Biogerontology 5:421–429PubMedCrossRef
77.
Kelly KA, Gimble JM (1998) 1,25-Dihydroxy vitamin D3 inhibits adipocyte differentiation and gene expression in murine bone marrow stromal cell clones and primary cultures. Endocrinology 39:2622–2628
78.
Cianferotti L, Demay MB (2007) VDR-mediated inhibition of DKK1 and SFRP2 suppresses adipogenic differentiation of murine bone marrow stromal cells. J Cell Biochem 101:80–88PubMedCrossRef
79.
Nimitphong H, Holick MF, Fried SK et al (2012) 25-Hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 promote the differentiation of human subcutaneous preadipocytes. PLoS ONE 7:e52171PubMedCentralPubMedCrossRef
80.
Zhang S, Chan M, Aubin JE (2006) Pleiotropic effects of the steroid hormone 1,25-dihydroxyvitamin D3 on the recruitment of mesenchymal lineage progenitors in fetal rat calvaria cell populations. J Mol Endocrinol 36:425–433PubMedCrossRef
81.
Ding J, Nagai K, Woo JT (2003) Insulin-dependent adipogenesis in stromal ST2 cells derived from murine bone marrow. Biosci Biotechnol Biochem 67:314–321PubMedCrossRef
82.
Lee JS, Park JH, Kwon IK et al (2011) Retinoic acid inhibits BMP4-induced C3H10T1/2 stem cell commitment to adipocyte via downregulating Smad/p38MAPK signaling. Biochem Biophys Res Commun 409:550–555PubMedCrossRef
83.
Skillington J, Choy L, Derynck R (2002) Bone morphogenetic protein and retinoic acid signaling cooperate to induce osteoblast differentiation of preadipocytes. J Cell Biol 159:135–146PubMedCrossRef
84.
Dingwall M, Marchildon F, Gunanayagam A et al (2011) Retinoic acid-induced Smad3 expression is required for the induction of osteoblastogenesis of mesenchymal stem cells. Differentiation 82:57–65PubMedCrossRef
85.
Zvonic S, Ptitsyn AA, Conrad SA et al (2006) Characterization of peripheral circadian clocks in adipose tissues. Diabetes 55:962–970PubMedCrossRef
86.
Zvonic S, Ptitsyn AA, Kilroy G et al (2007) Circadian oscillation of gene expression in murine calvarial bone. J Bone Miner Res 22:357–365PubMedCrossRef
87.
Otway DT, Mantele S, Bretschneider S et al (2011) Rhythmic diurnal gene expression in human adipose tissue from individuals who are lean, overweight, and have type 2 diabetes. Diabetes 60:1577–1581PubMedCrossRef
88.
Wu X, Zvonic S, Floyd ZE et al (2007) Induction of circadian gene expression in human subcutaneous adipose-derived stem cells. Obesity (Silver Spring) 15:2560–2570CrossRef
89.
90.
Wu X, Yu G, Parks H et al (2008) Circadian mechanisms in murine and human bone marrow mesenchymal stem cells following dexamethasone exposure. Bone 42:861–870PubMedCentralPubMedCrossRef
91.
Shimba S, Ishii N, Ohta Y et al (2005) Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis. Proc Natl Acad Sci USA 102:12071–12076PubMedCrossRef
92.
Kumar N, Solt LA, Wang Y et al (2010) Regulation of adipogenesis by natural and synthetic REV-ERB ligands. Endocrinology 151:3015–3025PubMedCrossRef
93.
Chawla A, Lazar MA (1993) Induction of Rev-ErbA alpha, an orphan receptor encoded on the opposite strand of the alpha-thyroid hormone receptor gene, during adipocyte differentiation. J Biol Chem 268:16265–16269PubMed
94.
Shi X, Shi W, Li Q et al (2003) A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells. EMBO Rep 4:374–380PubMedCentralPubMedCrossRef
95.
Gimble JM, Ptitsyn AA, Goh BC et al (2009) Delta sleep-inducing peptide and glucocorticoid-induced leucine zipper: potential links between circadian mechanisms and obesity? Obes Rev 10(Suppl 2):46–51PubMedCrossRef
96.
Zhang W, Yang N, Shi XM (2008) Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ). J Biol Chem 283:4723–4729PubMedCrossRef
97.
Lemberger T, Saladin R, Vazquez M et al (1996) Expression of the peroxisome proliferator-activated receptor alpha gene is stimulated by stress and follows a diurnal rhythm. J Biol Chem 271:1764–1769PubMedCrossRef
98.
Matsumoto E, Ishihara A, Tamai S et al (2010) Time of day and nutrients in feeding govern daily expression rhythms of the gene for sterol regulatory element-binding protein (SREBP)-1 in the mouse liver. J Biol Chem 285:33028–33036PubMedCrossRef
99.
Brewer M, Lange D, Baler R et al (2005) SREBP-1 as a transcriptional integrator of circadian and nutritional cues in the liver. J Biol Rhythms 20:195–205PubMedCrossRef
100.
Baggs JE, Green CB (2003) Nocturnin, a deadenylase in Xenopus laevis retina: a mechanism for posttranscriptional control of circadian-related mRNA. Curr Biol 13:189–198PubMedCrossRef
101.
Kawai M, Delany AM, Green CB et al (2010) Nocturnin suppresses igf1 expression in bone by targeting the 3′ untranslated region of igf1 mRNA. Endocrinology 151:4861–4870PubMedCrossRef
102.
Kawai M, Green CB, Lecka-Czernik B et al (2010) A circadian-regulated gene, Nocturnin, promotes adipogenesis by stimulating PPAR-gamma nuclear translocation. Proc Natl Acad Sci USA 107:10508–10513PubMedCrossRef
103.
Guntur AR, Kawai M, Le P et al (2011) An essential role for the circadian-regulated gene nocturnin in osteogenesis: the importance of local timekeeping in skeletal homeostasis. Ann N Y Acad Sci 1237:58–63PubMedCentralPubMedCrossRef
104.
105.
Li Y, He X, He J et al (2011) Nicotinamide phosphoribosyltransferase (Nampt) affects the lineage fate determination of mesenchymal stem cells: a possible cause for reduced osteogenesis and increased adipogenesis in older individuals. J Bone Miner Res 26:2656–2664PubMedCrossRef
106.
Gimble JM, Sutton GM, Bunnell BA, Ptitsyn AA, Floyd ZE (2011) Prospective influences of circadian clocks in adipose tissue and metabolism. Nat Rev Endocrinol 7:98–107PubMedCrossRef
107.
Machida M, Dubousset J, Imamura Y et al (1993) An experimental study in chickens for the pathogenesis of idiopathic scoliosis. Spine (Phila Pa 1976) 18:1609–1615CrossRef
108.
Brydon L, Petit L, Delagrange P, Strosberg AD, Jockers R (2001) Functional expression of MT2 (Mel1b) melatonin receptors in human PAZ6 adipocytes. Endocrinology 142:4264–4271PubMed
109.
Bartness TJ, Goldman BD (1988) Peak duration of serum melatonin and short-day responses in adult Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 255:R812–R822
110.
111.
Halaas JL, Gajiwala KS, Maffei M et al (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543–546PubMedCrossRef
112.
Baumann H, Morella KK, White DW et al (1996) The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc Natl Acad Sci USA 93:8374–8378PubMedCrossRef
113.
Thomas T, Gori F, Khosla S et al (1999) Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology 140:1630–1638PubMed
114.
Bartell SM, Rayalam S, Ambati S et al (2011) Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice. J Bone Miner Res 26:1710–1720PubMedCrossRef
115.
Williams GA, Callon KE, Watson M et al (2011) Skeletal phenotype of the leptin receptor-deficient db/db mouse. J Bone Miner Res 26:1698–1709PubMedCrossRef
116.
Hamrick MW, Della-Fera MA, Choi YH et al (2005) Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. J Bone Miner Res 20:994–1001PubMedCrossRef
117.
Ducy P, Amling M, Takeda S et al (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100:197–207PubMedCrossRef
118.
Takeda S, Elefteriou F, Levasseur R et al (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305–317PubMedCrossRef
119.
Elefteriou F, Takeda S, Ebihara K et al (2004) Serum leptin level is a regulator of bone mass. Proc Natl Acad Sci USA 101:3258–3263PubMedCrossRef
120.
Elefteriou F, Ahn JD, Takeda S et al (2005) Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434:514–520PubMedCrossRef
121.
Sims NA, Walsh NC (2010) GP130 cytokines and bone remodelling in health and disease. BMB Rep 43:513–523PubMedCrossRef
122.
Gimble JM, Wanker F, Wang CS et al (1994) Regulation of bone marrow stromal cell differentiation by cytokines whose receptors share the gp130 protein. J Cell Biochem 54:122–133PubMedCrossRef
123.
124.
125.
Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA 105:5266–5270PubMedCrossRef
126.
Rubin CT, Capilla E, Luu YK et al (2007) Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals. Proc Natl Acad Sci USA 104:17879–17884PubMedCrossRef
127.
Luu YK, Capilla E, Rosen CJ et al (2009) Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. J Bone Miner Res 24:50–61PubMedCrossRef
128.
Luu YK, Pessin JE, Judex S, Rubin J, Rubin CT (2009) Mechanical signals as a non-invasive means to influence mesenchymal stem cell fate, promoting bone and suppressing the fat phenotype. Bonekey Osteovision 6:132–149PubMedCentralPubMed
129.
Charoenpanich A, Wall ME, Tucker CJ et al (2011) Microarray analysis of human adipose-derived stem cells in three-dimensional collagen culture: osteogenesis inhibits bone morphogenic protein and Wnt signaling pathways, and cyclic tensile strain causes upregulation of proinflammatory cytokine regulators and angiogenic factors. Tissue Eng Part A 17:2615–2627PubMedCrossRef
130.
Bredella MA, Fazeli PK, Miller KK et al (2009) Increased bone marrow fat in anorexia nervosa. J Clin Endocrinol Metab 94:2129–2136PubMedCrossRef
131.
Burris TP (2008) Nuclear hormone receptors for heme: REV-ERBalpha and REV-ERBbeta are ligand-regulated components of the mammalian clock. Mol Endocrinol 22:1509–1520PubMedCrossRef
132.
Shore EM, Ahn J, Jan de Beur S et al (2002) Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia. N Engl J Med 346:99–106PubMedCrossRef
133.
Davis TA, O’Brien FP, Anam K et al (2011) Heterotopic ossification in complex orthopaedic combat wounds: quantification and characterization of osteogenic precursor cell activity in traumatized muscle. J Bone Joint Surg Am 93:1122–1131PubMed
134.
Shore EM, Kaplan FS (2011) Role of altered signal transduction in heterotopic ossification and fibrodysplasia ossificans progressiva. Curr Osteoporos Rep 9:83–88PubMedCentralPubMedCrossRef
135.
Cheng SL, Shao JS, Charlton-Kachigian N et al (2003) MSX2 promotes osteogenesis and suppresses adipogenic differentiation of multipotent mesenchymal progenitors. J Biol Chem 278:45969–45977PubMedCrossRef
136.
Tontonoz P, Kim JB, Graves RA et al (1993) ADD1: a novel helix–loop–helix transcription factor associated with adipocyte determination and differentiation. Mol Cell Biol 13:4753–4759PubMedCentralPubMed
137.
Isenmann S, Arthur A, Zannettino AC et al (2009) TWIST family of basic helix–loop–helix transcription factors mediate human mesenchymal stem cell growth and commitment. Stem Cells 27:2457–2468PubMedCrossRef
138.
Oishi Y, Manabe I, Tobe K et al (2005) Kruppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation. Cell Metab 1:27–39PubMedCrossRef
139.
Chen Z, Torrens JI, Anand A et al (2005) Krox20 stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms. Cell Metab 1:93–106PubMedCrossRef
140.
You L, Pan L, Chen L et al (2012) Suppression of zinc finger protein 467 alleviates osteoporosis through promoting differentiation of adipose derived stem cells to osteoblasts. J Transl Med 10:11PubMedCentralPubMedCrossRef
141.
Wu Z, Puigserver P, Andersson U et al (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124PubMedCrossRef
142.
Shi H, Norman AW, Okamura WH et al (2001) 1α25-Dihydroxyvitamin D3 modulates human adipocyte metabolism via nongenomic action. FASEB J 15:2751–2753PubMed
143.
Liu J, Farmer SR (2004) Regulating the balance between peroxisome proliferator-activated receptor gamma and beta-catenin signaling during adipogenesis. A glycogen synthase kinase 3beta phosphorylation-defective mutant of beta-catenin inhibits expression of a subset of adipogenic genes. J Biol Chem 279:45020–45027PubMedCrossRef
144.
145.
Zhou S, Lechpammer S, Greenberger JS et al (2005) Hypoxia inhibition of adipocytogenesis in human bone marrow stromal cells requires transforming growth factor-beta/Smad3 signaling. J Biol Chem 280:22688–22696PubMedCentralPubMedCrossRef
146.
Xu Y, Takahashi Y, Wang Y et al (2009) Downregulation of GATA-2 and overexpression of adipogenic gene-PPARgamma in mesenchymal stem cells from patients with aplastic anemia. Exp Hematol 37:1393–1399PubMedCrossRef
147.
Zhang X, Yang M, Lin L et al (2006) Runx2 overexpression enhances osteoblastic differentiation and mineralization in adipose-derived stem cells in vitro and in vivo. Calcif Tissue Int 79:169–178PubMedCrossRef
148.
Liu LF, Shen WJ, Zhang ZH et al (2010) Adipocytes decrease Runx2 expression in osteoblastic cells: roles of PPARgamma and adiponectin. J Cell Physiol 225:837–845PubMedCrossRef
149.
Geoffroy V, Ducy P, Karsenty G (1995) A PEBP2 alpha/AML-1-related factor increases osteocalcin promoter activity through its binding to an osteoblast-specific cis-acting element. J Biol Chem 270:30973–30979PubMedCrossRef
150.
Hong JH, Hwang ES, McManus MT et al (2005) TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science 309:1074–1078PubMedCrossRef
151.
Hong JH, Yaffe MB (2006) TAZ: a beta-catenin-like molecule that regulates mesenchymal stem cell differentiation. Cell Cycle 5:176–179PubMedCrossRef
Metadata
Title
Adipocytes and the Regulation of Bone Remodeling: A Balancing Act
Authors
Mark E. Nuttall
Forum Shah
Vikramjeet Singh
Caasy Thomas-Porch
Trivia Frazier
Jeffrey M. Gimble
Publication date
01-01-2014
Publisher
Springer US
Published in
Calcified Tissue International / Issue 1/2014
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-013-9807-6

Other articles of this Issue 1/2014

Calcified Tissue International 1/2014 Go to the issue

Review

Cellular Complexity of the Bone Marrow Hematopoietic Stem Cell Niche

Original Research

Osteoclast-Derived Coupling Factors in Bone Remodeling

Erratum

Erratum to: Cell–Cell Signaling: Broadening Our View of the Basic Multicellular Unit

Original Research

Cadherin-Mediated Cell–Cell Adhesion and Signaling in the Skeleton

Review

Signaling Between Tumor Cells and the Host Bone Marrow Microenvironment

Editorial

Calcified Tissue International—“The Times, They are a-Changin’”
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits