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Published in: Current Osteoporosis Reports 2/2010

01-06-2010

PPARs in Bone: The Role in Bone Cell Differentiation and Regulation of Energy Metabolism

Author: Beata Lecka-Czernik

Published in: Current Osteoporosis Reports | Issue 2/2010

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Abstract

Obesity, diabetes, and osteoporosis are major public health concerns. Current estimates indicate that the US population consists of 25% obese, 30% diabetic and prediabetic, and, among the elderly, 50% of all osteoporotic individuals. Mechanistically, these pathologies share several features including common regulators of bone homeostasis and energy metabolism. Peroxisome proliferator-activated receptors (PPARs) represent a family of proteins that control energy turnover in adipose, liver, and muscle tissue. These proteins also control bone turnover and regulate bone cell differentiation. Recent evidence suggests that bone is an organ integral to energy metabolism not only with respect to energy storage, but also as an organ regulating systemic energy homeostasis. In this article, we review current knowledge on the role of PPARs in bone metabolism and bone cell differentiation. We also discuss the role of bone fat in modulation of bone marrow microenvironment and its possible contribution to the systemic regulation of energy metabolism.
Literature
1.
go back to reference • Lee NK, Sowa H, Hinoi E, et al.: Endocrine regulation of energy metabolism by the skeleton. Cell 2007, 130:456–469. This study demonstrates for the first time that bone-derived osteocalcin hormone regulates energy metabolism.CrossRefPubMed • Lee NK, Sowa H, Hinoi E, et al.: Endocrine regulation of energy metabolism by the skeleton. Cell 2007, 130:456–469. This study demonstrates for the first time that bone-derived osteocalcin hormone regulates energy metabolism.CrossRefPubMed
2.
go back to reference Hinoi E, Gao N, Jung DY, et al.: An osteoblast-dependent mechanism contributes to the leptin regulation of insulin secretion. Ann N Y Acad Sci 2009, 1173(Suppl 1):E20–E30.CrossRefPubMed Hinoi E, Gao N, Jung DY, et al.: An osteoblast-dependent mechanism contributes to the leptin regulation of insulin secretion. Ann N Y Acad Sci 2009, 1173(Suppl 1):E20–E30.CrossRefPubMed
3.
go back to reference Bianco P, Riminucci M, Gronthos S, Robey PG: Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 2001, 19:180–192.CrossRefPubMed Bianco P, Riminucci M, Gronthos S, Robey PG: Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 2001, 19:180–192.CrossRefPubMed
4.
go back to reference Lecka-Czernik B, Suva LJ: Resolving the two “bony” faces of PPAR-gamma. PPAR Res 2006, 2006:27489. Lecka-Czernik B, Suva LJ: Resolving the two “bony” faces of PPAR-gamma. PPAR Res 2006, 2006:27489.
5.
go back to reference Evans RM, Barish GD, Wang YX: PPARs and the complex journey to obesity. Nat Med 2004, 10:355–361.CrossRefPubMed Evans RM, Barish GD, Wang YX: PPARs and the complex journey to obesity. Nat Med 2004, 10:355–361.CrossRefPubMed
6.
go back to reference Zoete V, Grosdidier A, Michielin O: Peroxisome proliferator-activated receptor structures: ligand specificity, molecular switch and interactions with regulators. Biochim Biophys Acta 2007, 1771:915–925.PubMed Zoete V, Grosdidier A, Michielin O: Peroxisome proliferator-activated receptor structures: ligand specificity, molecular switch and interactions with regulators. Biochim Biophys Acta 2007, 1771:915–925.PubMed
7.
go back to reference Tontonoz P, Spiegelman BM: Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem 2008, 77:289–312.CrossRefPubMed Tontonoz P, Spiegelman BM: Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem 2008, 77:289–312.CrossRefPubMed
8.
go back to reference Heikkinen S, Auwerx J, Argmann CA: PPARgamma in human and mouse physiology. Biochim Biophys Acta 2007, 1771:999–1013.PubMed Heikkinen S, Auwerx J, Argmann CA: PPARgamma in human and mouse physiology. Biochim Biophys Acta 2007, 1771:999–1013.PubMed
9.
go back to reference Ren D, Collingwood TN, Rebar EJ, et al.: PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis. Genes Dev 2002, 16:27–32.CrossRefPubMed Ren D, Collingwood TN, Rebar EJ, et al.: PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis. Genes Dev 2002, 16:27–32.CrossRefPubMed
10.
go back to reference Lecka-Czernik B, Gubrij I, Moerman EA, et al.: Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPAR-gamma 2. J Cell Biochem 1999, 74:357–371.CrossRefPubMed Lecka-Czernik B, Gubrij I, Moerman EA, et al.: Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPAR-gamma 2. J Cell Biochem 1999, 74:357–371.CrossRefPubMed
11.
go back to reference Willson TM, Lambert MH, Kliewer SA: Peroxisome proliferator-activated receptor gamma and metabolic disease. Annu Rev Biochem 2001, 70:341–367.CrossRefPubMed Willson TM, Lambert MH, Kliewer SA: Peroxisome proliferator-activated receptor gamma and metabolic disease. Annu Rev Biochem 2001, 70:341–367.CrossRefPubMed
12.
go back to reference Knouff C, Auwerx J: Peroxisome proliferator-activated receptor-gamma calls for activation in moderation: lessons from genetics and pharmacology. Endocr Rev 2004, 25:899–918.CrossRefPubMed Knouff C, Auwerx J: Peroxisome proliferator-activated receptor-gamma calls for activation in moderation: lessons from genetics and pharmacology. Endocr Rev 2004, 25:899–918.CrossRefPubMed
13.
go back to reference Lecka-Czernik B, Moerman EJ, Grant DF, et al.: Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology 2002, 143:2376–2384.CrossRefPubMed Lecka-Czernik B, Moerman EJ, Grant DF, et al.: Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology 2002, 143:2376–2384.CrossRefPubMed
14.
go back to reference Wan Y, Chong LW, Evans RM: PPAR-gamma regulates osteoclastogenesis in mice. Nat Med 2007, 13:1496–1503.CrossRefPubMed Wan Y, Chong LW, Evans RM: PPAR-gamma regulates osteoclastogenesis in mice. Nat Med 2007, 13:1496–1503.CrossRefPubMed
15.
go back to reference Rzonca SO, Suva LJ, Gaddy D, et al.: Bone is a target for the antidiabetic compound rosiglitazone. Endocrinology 2004, 145:401–406.CrossRefPubMed Rzonca SO, Suva LJ, Gaddy D, et al.: Bone is a target for the antidiabetic compound rosiglitazone. Endocrinology 2004, 145:401–406.CrossRefPubMed
16.
go back to reference • Lazarenko OP, Rzonca SO, Hogue WR, et al.: Rosiglitazone induces decreases in bone mass and strength that are reminiscent of aged bone. Endocrinology 2007, 148:2669–2680. This article shows that aging is a confounding factor for rosiglitazone-induced bone loss in mice.CrossRefPubMed • Lazarenko OP, Rzonca SO, Hogue WR, et al.: Rosiglitazone induces decreases in bone mass and strength that are reminiscent of aged bone. Endocrinology 2007, 148:2669–2680. This article shows that aging is a confounding factor for rosiglitazone-induced bone loss in mice.CrossRefPubMed
17.
go back to reference Akune T, Ohba S, Kamekura S, et al.: PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest 2004, 113:846–855.PubMed Akune T, Ohba S, Kamekura S, et al.: PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest 2004, 113:846–855.PubMed
18.
go back to reference Rosen CJ, Bouxsein ML: Mechanism of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol 2006, 2:35–43.CrossRefPubMed Rosen CJ, Bouxsein ML: Mechanism of disease: is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol 2006, 2:35–43.CrossRefPubMed
19.
go back to reference Moerman EJ, Teng K, Lipschitz DA, Lecka-Czernik B: Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell 2004, 3:379–389.CrossRefPubMed Moerman EJ, Teng K, Lipschitz DA, Lecka-Czernik B: Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell 2004, 3:379–389.CrossRefPubMed
20.
go back to reference Spiteller G: The important role of lipid peroxidation processes in aging and age dependent diseases. Mol Biotechnol 2007, 37:5–12.CrossRefPubMed Spiteller G: The important role of lipid peroxidation processes in aging and age dependent diseases. Mol Biotechnol 2007, 37:5–12.CrossRefPubMed
21.
go back to reference Maurin AC, Chavassieux PM, Vericel E, Meunier PJ: Role of polyunsaturated fatty acids in the inhibitory effect of human adipocytes on osteoblastic proliferation. Bone 2002, 31:260–266.CrossRefPubMed Maurin AC, Chavassieux PM, Vericel E, Meunier PJ: Role of polyunsaturated fatty acids in the inhibitory effect of human adipocytes on osteoblastic proliferation. Bone 2002, 31:260–266.CrossRefPubMed
22.
go back to reference • Shockley KR, Rosen CJ, Churchill GA, Lecka-Czernik B: PPARγ2 regulates a molecular signature of marrow mesenchymal stem cells. PPAR Research 2007, 2007:81219. This article demonstrates that PPAR-γ2 plays a major role in regulation of MSC "stemness" phenotype.CrossRefPubMed • Shockley KR, Rosen CJ, Churchill GA, Lecka-Czernik B: PPARγ2 regulates a molecular signature of marrow mesenchymal stem cells. PPAR Research 2007, 2007:81219. This article demonstrates that PPAR-γ2 plays a major role in regulation of MSC "stemness" phenotype.CrossRefPubMed
23.
go back to reference Minaire P, Edouard C, Arlot M, Meunier PJ: Marrow changes in paraplegic patients. Calcif Tissue Int 1984, 36:338–340.CrossRefPubMed Minaire P, Edouard C, Arlot M, Meunier PJ: Marrow changes in paraplegic patients. Calcif Tissue Int 1984, 36:338–340.CrossRefPubMed
24.
go back to reference Trudel G, Payne M, Madler B, et al.: Bone marrow fat accumulation after 60 days of bed rest persisted 1 year after activities were resumed along with hemopoietic stimulation: the Women International Space Simulation for Exploration study. J Appl Physiol 2009, 107:540–548.CrossRefPubMed Trudel G, Payne M, Madler B, et al.: Bone marrow fat accumulation after 60 days of bed rest persisted 1 year after activities were resumed along with hemopoietic stimulation: the Women International Space Simulation for Exploration study. J Appl Physiol 2009, 107:540–548.CrossRefPubMed
25.
go back to reference Suva LJ, Gaddy D, Perrien DS, et al.: Regulation of bone mass by mechanical loading: microarchitecture and genetics. Curr Osteoporos Rep 2005, 3:46–51.CrossRefPubMed Suva LJ, Gaddy D, Perrien DS, et al.: Regulation of bone mass by mechanical loading: microarchitecture and genetics. Curr Osteoporos Rep 2005, 3:46–51.CrossRefPubMed
26.
go back to reference Marie PJ, Kaabeche K: PPAR gamma and control of bone mass in skeletal unloading. PPAR Res 2006, 2006:64807.PubMed Marie PJ, Kaabeche K: PPAR gamma and control of bone mass in skeletal unloading. PPAR Res 2006, 2006:64807.PubMed
27.
go back to reference Cock TA, Back J, Elefteriou F, et al.: Enhanced bone formation in lipodystrophic PPARgamma(hyp/hyp) mice relocates haematopoiesis to the spleen. EMBO Rep 2004, 5:1007–1012.CrossRefPubMed Cock TA, Back J, Elefteriou F, et al.: Enhanced bone formation in lipodystrophic PPARgamma(hyp/hyp) mice relocates haematopoiesis to the spleen. EMBO Rep 2004, 5:1007–1012.CrossRefPubMed
28.
go back to reference Ali AA, Weinstein RS, Stewart SA, et al.: Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation. Endocrinology 2005, 146:1226–1235.CrossRefPubMed Ali AA, Weinstein RS, Stewart SA, et al.: Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation. Endocrinology 2005, 146:1226–1235.CrossRefPubMed
29.
go back to reference Sottile V, Seuwen K, Kneissel M: Enhanced marrow adipogenesis and bone resorption in estrogen-deprived rats treated with the PPARgamma agonist BRL49653 (rosiglitazone). Calcif Tissue Int 2004, 75:329–337.CrossRefPubMed Sottile V, Seuwen K, Kneissel M: Enhanced marrow adipogenesis and bone resorption in estrogen-deprived rats treated with the PPARgamma agonist BRL49653 (rosiglitazone). Calcif Tissue Int 2004, 75:329–337.CrossRefPubMed
30.
go back to reference Modder UI, Monroe DG, Fraser DG, et al.: Skeletal consequences of deletion of steroid receptor coactivator-2/transcription intermediary factor-2. J Biol Chem 2009, 284:18767–18777.CrossRefPubMed Modder UI, Monroe DG, Fraser DG, et al.: Skeletal consequences of deletion of steroid receptor coactivator-2/transcription intermediary factor-2. J Biol Chem 2009, 284:18767–18777.CrossRefPubMed
31.
go back to reference • Shockley KR, Lazarenko OP, Czernik PJ, et al.: PPARγ2 nuclear receptor controls multiple regulatory pathways of osteoblast differentiation from marrow mesenchymal stem cells. J Cell Biochem 2009, 106:232–246. This article provides an extensive analysis of the effect of rosiglitazone on gene expression in marrow MSCs.CrossRefPubMed • Shockley KR, Lazarenko OP, Czernik PJ, et al.: PPARγ2 nuclear receptor controls multiple regulatory pathways of osteoblast differentiation from marrow mesenchymal stem cells. J Cell Biochem 2009, 106:232–246. This article provides an extensive analysis of the effect of rosiglitazone on gene expression in marrow MSCs.CrossRefPubMed
32.
go back to reference Lecka-Czernik B: Bone as a target of type 2 diabetes treatment. Curr Opin Investig Drugs 2009, 10:1085–1090.PubMed Lecka-Czernik B: Bone as a target of type 2 diabetes treatment. Curr Opin Investig Drugs 2009, 10:1085–1090.PubMed
33.
go back to reference • Kahn SE, Zinman B, Lachin JM, et al.: Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT). Diabetes Care 2008, 31:845–851. This article provides a retrospective analysis of fracture risk and type of fractures among the ADOPT participants.CrossRefPubMed • Kahn SE, Zinman B, Lachin JM, et al.: Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT). Diabetes Care 2008, 31:845–851. This article provides a retrospective analysis of fracture risk and type of fractures among the ADOPT participants.CrossRefPubMed
34.
go back to reference • Loke YK, Singh S, Furberg CD: Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ 2009, 180:32–39. This article provides a comprehensive review of available clinical trials in respect to the effect of TZDs on risk of fractures.PubMed • Loke YK, Singh S, Furberg CD: Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ 2009, 180:32–39. This article provides a comprehensive review of available clinical trials in respect to the effect of TZDs on risk of fractures.PubMed
35.
go back to reference Meier C, Kraenzlin ME, Bodmer M, et al.: Use of thiazolidinediones and fracture risk. Arch Intern Med 2008, 168:820–825.CrossRefPubMed Meier C, Kraenzlin ME, Bodmer M, et al.: Use of thiazolidinediones and fracture risk. Arch Intern Med 2008, 168:820–825.CrossRefPubMed
36.
go back to reference Lefebvre P, Chinetti G, Fruchart JC, Staels B: Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J Clin Invest 2006, 116:571–580.CrossRefPubMed Lefebvre P, Chinetti G, Fruchart JC, Staels B: Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J Clin Invest 2006, 116:571–580.CrossRefPubMed
37.
go back to reference Remick J, Weintraub H, Setton R, et al.: Fibrate therapy: an update. Cardiol Rev 2008, 16:129–141. Remick J, Weintraub H, Setton R, et al.: Fibrate therapy: an update. Cardiol Rev 2008, 16:129–141.
38.
go back to reference Giaginis C, Tsantili-Kakoulidou A, Theocharis S: Peroxisome proliferator-activated receptors (PPARs) in the control of bone metabolism. Fundam Clin Pharmacol 2007, 21:231–244.CrossRefPubMed Giaginis C, Tsantili-Kakoulidou A, Theocharis S: Peroxisome proliferator-activated receptors (PPARs) in the control of bone metabolism. Fundam Clin Pharmacol 2007, 21:231–244.CrossRefPubMed
39.
go back to reference Wu X, Peters JM, Gonzalez FJ, et al.: Frequency of stromal lineage colony forming units in bone marrow of peroxisome proliferator-activated receptor-alpha-null mice. Bone 2000, 26:21–26.CrossRefPubMed Wu X, Peters JM, Gonzalez FJ, et al.: Frequency of stromal lineage colony forming units in bone marrow of peroxisome proliferator-activated receptor-alpha-null mice. Bone 2000, 26:21–26.CrossRefPubMed
40.
go back to reference Yang Q, Gonzalez FJ: Peroxisome proliferator-activated receptor alpha regulates B lymphocyte development via an indirect pathway in mice. Biochem Pharmacol 2004, 68:2143–2150.CrossRefPubMed Yang Q, Gonzalez FJ: Peroxisome proliferator-activated receptor alpha regulates B lymphocyte development via an indirect pathway in mice. Biochem Pharmacol 2004, 68:2143–2150.CrossRefPubMed
41.
go back to reference Still K, Grabowski P, Mackie I, et al.: The peroxisome proliferator activator receptor alpha/delta agonists linoleic acid and bezafibrate upregulate osteoblast differentiation and induce periosteal bone formation in vivo. Calcif Tissue Int 2008, 83:285–292.CrossRefPubMed Still K, Grabowski P, Mackie I, et al.: The peroxisome proliferator activator receptor alpha/delta agonists linoleic acid and bezafibrate upregulate osteoblast differentiation and induce periosteal bone formation in vivo. Calcif Tissue Int 2008, 83:285–292.CrossRefPubMed
42.
go back to reference Chan BY, Gartland A, Wilson PJ, et al.: PPAR agonists modulate human osteoclast formation and activity in vitro. Bone 2007, 40:149–159.CrossRefPubMed Chan BY, Gartland A, Wilson PJ, et al.: PPAR agonists modulate human osteoclast formation and activity in vitro. Bone 2007, 40:149–159.CrossRefPubMed
43.
go back to reference Syversen U, Stunes AK, Gustafsson BI, et al.: Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)alpha agonist fenofibrate and the PPARgamma agonist pioglitazone. BMC Endocr Disord 2009, 9:10.CrossRefPubMed Syversen U, Stunes AK, Gustafsson BI, et al.: Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)alpha agonist fenofibrate and the PPARgamma agonist pioglitazone. BMC Endocr Disord 2009, 9:10.CrossRefPubMed
44.
go back to reference Meier CR, Schlienger RG, Kraenzlin ME, et al.: HMG-CoA reductase inhibitors and the risk of fractures. JAMA 2000, 283:3205–3210.CrossRefPubMed Meier CR, Schlienger RG, Kraenzlin ME, et al.: HMG-CoA reductase inhibitors and the risk of fractures. JAMA 2000, 283:3205–3210.CrossRefPubMed
45.
go back to reference Barish GD, Narkar VA, Evans RM: PPAR delta: a dagger in the heart of the metabolic syndrome. J Clin Invest 2006, 116:590–597.CrossRefPubMed Barish GD, Narkar VA, Evans RM: PPAR delta: a dagger in the heart of the metabolic syndrome. J Clin Invest 2006, 116:590–597.CrossRefPubMed
46.
go back to reference Wang YX, Lee CH, Tiep S, et al.: Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell 2003, 113:159–170.CrossRefPubMed Wang YX, Lee CH, Tiep S, et al.: Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell 2003, 113:159–170.CrossRefPubMed
47.
go back to reference Gimble JM, Zvonic S, Floyd ZE, et al.: Playing with bone and fat. J Cell Biochem 2006, 98:251–266.CrossRefPubMed Gimble JM, Zvonic S, Floyd ZE, et al.: Playing with bone and fat. J Cell Biochem 2006, 98:251–266.CrossRefPubMed
48.
go back to reference Tavassoli M: Marrow adipose cells and hemopoiesis: an interpretative review. Exp Hematol 1984, 12:139–146.PubMed Tavassoli M: Marrow adipose cells and hemopoiesis: an interpretative review. Exp Hematol 1984, 12:139–146.PubMed
49.
go back to reference Elefteriou F, Ahn JD, Takeda S, et al.: Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 2005, 434:514–520.CrossRefPubMed Elefteriou F, Ahn JD, Takeda S, et al.: Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 2005, 434:514–520.CrossRefPubMed
50.
go back to reference Shinoda Y, Yamaguchi M, Ogata N, et al.: Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell Biochem 2006, 99:196–208.CrossRefPubMed Shinoda Y, Yamaguchi M, Ogata N, et al.: Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell Biochem 2006, 99:196–208.CrossRefPubMed
51.
go back to reference Cartwright MJ, Tchkonia T, Kirkland JL: Aging in adipocytes: potential impact of inherent, depot-specific mechanisms. Exp Gerontol 2007, 42:463–471.CrossRefPubMed Cartwright MJ, Tchkonia T, Kirkland JL: Aging in adipocytes: potential impact of inherent, depot-specific mechanisms. Exp Gerontol 2007, 42:463–471.CrossRefPubMed
52.
go back to reference Gasparrini M, Rivas D, Elbaz A, Duque G: Differential expression of cytokines in subcutaneous and marrow fat of aging C57BL/6 J mice. Exp Gerontol 2009, 44:613–618.CrossRefPubMed Gasparrini M, Rivas D, Elbaz A, Duque G: Differential expression of cytokines in subcutaneous and marrow fat of aging C57BL/6 J mice. Exp Gerontol 2009, 44:613–618.CrossRefPubMed
Metadata
Title
PPARs in Bone: The Role in Bone Cell Differentiation and Regulation of Energy Metabolism
Author
Beata Lecka-Czernik
Publication date
01-06-2010
Publisher
Current Science Inc.
Published in
Current Osteoporosis Reports / Issue 2/2010
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-010-0016-1

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