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Osteosarcopenia: Bone, Muscle and Fat Interactions pp 29–44Cite as

Mesenchymal Stem Cells as Regulators of Bone, Muscle, and Fat Formation

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Abstract

The controversial concept of a “mesenchymal stem cell”, also known as “multipotent stromal cell” or “MSC”, has served as a cell biological foundation upon which to build and test hypotheses examining the complex relationships between bone, fat and skeletal muscle. Multiple independent studies have demonstrated the presence of MSC-like cells within connective tissues including bone, fascia, fat, marrow, skeletal muscle, and tendon. The MSC has been defined based on its plastic adherence and proliferative properties in vitro, its trilineage (adipogenic, chondrogenic, and osteogenic) differentiation ability, and its distinctive surface immunophenotype. Moreover, the differentiated MSC adipocytes, myocytes and osteoblasts secrete distinct profiles of growth factors termed “adipokines”, “myokines” and “osteokines”. These “-kines”, which include both anti- and pro-inflammatory cytokines, account in part for the MSC’s immunomodulatory and immunosuppressive functions in vitro and in vivo. Recent studies have focused on the MSC’s secretion of microvesicular “exosomes” containing cytokines, adhesive surface proteins, and microRNAs capable of positively or negatively modulating lineage specific signal transduction pathways. This chapter reviews the history and recent discoveries relating MSCs to the biological aging-associated pathologies of obesity, osteoporosis, and sarcopenia.

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Abbreviations

ALK:

Activin-Like Receptor Kinase

AMPK:

5′ Adenosine Monophosphate Activated Protein Kinase

ASC:

Adipose-derived Stromal/Stem Cell

BAT:

Brown Adipose Tissue

BDNF:

Brain Derived Neurotrophic Factor

BMP:

Bone Morphogenetic Protein

BMSC:

Bone Marrow-derived Mesenchymal Stem Cell or Bone Marrow-derived Multipotent Stromal Cell

C/EBP:

CCAAT Enhancer Binding Protein

ER:

Estrogen Receptor

FDNC5:

Fibronectin Domain Containing Protein 5

FGF:

Fibroblast Growth Factor

GDF:

Growth and Differentiation Factor

GR:

Glucocorticoid Receptor

HLH:

Helix Loop Helix

IFATS:

International Federation for Adipose Therapeutics and Science

IGF-1:

Insulin like Growth Factor 1

IL:

Interleukine

IMAT:

Intramuscular Adipose Tissue

ISCT:

International Society for Cell & Gene Therapy

M-CSF:

Macrophage Colony Stimulating Factor

MEF:

Myocyte Enhancer Factor

miRNA:

Micro RNA

MSC:

Mesenchymal Stem Cell or Multipotent Stromal Cell

NFκB:

Nuclear Factor κ Light Chain Enhancer of Activated B Cells

NHR:

Nuclear Hormone Receptor

OCN:

Osteocalcin

PAI-1:

Plasminogen Activator Inhibitor 1

PEDF:

Pigment Epithelium Derived Factor

PGC1:

PPARγ Co-Activator 1

PPARγ:

Peroxisome Proliferator Activated Receptor γ

RANKL:

Receptor Activator for Nuclear Factor κ B Ligand

RUNX2:

Runt Related Transcription Factor 2

SMAD:

Small worm phenotype Mothers Against Decapentaplegic (BMP Transcription Factors)

SMSC:

Skeletal Muscle Stem Cell

SVF:

Stromal Vascular Fraction

TGFβ:

Transforming Growth Factor β

TNFα:

Tumor Necrosis Factor α

TRAP:

Tartrate Resistant Acid Phosphatase

VDR:

Vitamin D Receptor

WAT:

White Adipose Tissue

References

  • Allen TD, Dexter TM (1976) Cellular interrelationships during in vitro granulopoiesis. Diff Res Biol Diver 6:191–194

    CAS  Google Scholar 

  • Ashton BA, Allen TD, Howlett CR, Eaglesom CC, Hattori A, Owen M (1980) Formation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo. Clin Orthopaed Relat Res 151:294–307

    Google Scholar 

  • Becker C, Lord SR, Studenski SA, Warden SJ, Fielding RA, Recknor CP, Hochberg MC, Ferrari SL, Blain H, Binder EF, Rolland Y, Poiraudeau S, Benson CT, Myers SL, Hu L, Ahmad QI, Pacuch KR, Gomez EV, Benichou O, S. Group (2015) Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial. Lancet Diabetes Endocrinol 3:948–957

    Article  CAS  PubMed  Google Scholar 

  • Beresford JN, Bennett JH, Devlin C, Leboy PS, Owen ME (1992) Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J Cell Sci 102(Pt 2):341–351

    CAS  PubMed  Google Scholar 

  • Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Hojlund K, Gygi SP, Spiegelman BM (2012) A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481:463–468

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, Yoshimura K, Gimble JM (2013) Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 15:641–648

    Article  PubMed  PubMed Central  Google Scholar 

  • Braun T, Buschhausen-Denker G, Bober E, Tannich E, Arnold HH (1989) A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts. EMBO J 8:701–709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buehring B, Binkley N (2013) Myostatin--the holy grail for muscle, bone, and fat? Curr Osteoporos Rep 11:407–414

    Article  CAS  PubMed  Google Scholar 

  • Campbell C, McMillan HJ, Mah JK, Tarnopolsky M, Selby K, McClure T, Wilson DM, Sherman ML, Escolar D, Attie KM (2017) Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial. Muscle Nerve 55:458–464

    Article  CAS  PubMed  Google Scholar 

  • Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9:641–650

    Article  CAS  PubMed  Google Scholar 

  • Caplan AI, Correa D (2011) The MSC: an injury drugstore. Cell Stem Cell 9:11–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen L, Holmstrom K, Qiu W, Ditzel N, Shi K, Hokland L, Kassem M (2014) MicroRNA-34a inhibits osteoblast differentiation and in vivo bone formation of human stromal stem cells. Stem Cells 32:902–912

    Article  CAS  PubMed  Google Scholar 

  • Choi HY, Kim S, Park JW, Lee NS, Hwang SY, Huh JY, Hong HC, Yoo HJ, Baik SH, Youn BS, Mantzoros CS, Choi KM (2014) Implication of circulating irisin levels with brown adipose tissue and sarcopenia in humans. J Clin Endocrinol Metab 99:2778–2785

    Article  CAS  PubMed  Google Scholar 

  • Clark EA, Kalomoiris S, Nolta JA, Fierro FA (2014) Concise review: MicroRNA function in multipotent mesenchymal stromal cells. Stem Cells 32:1074–1082

    Article  CAS  PubMed  Google Scholar 

  • Colaianni G, Mongelli T, Colucci S, Cinti S, Grano M (2016) Crosstalk Between Muscle and Bone Via the Muscle-Myokine Irisin. Curr Osteoporos Rep 14:132–137

    Article  CAS  PubMed  Google Scholar 

  • D’Ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA (1999) Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. J Bone Miner Res 14:1115–1122

    Article  PubMed  Google Scholar 

  • Dennison EM, Sayer AA, Cooper C (2017) Epidemiology of sarcopenia and insight into possible therapeutic targets. Nat Rev Rheumatol 13:340–347

    Article  CAS  PubMed  Google Scholar 

  • Dexter TM, Allen TD, Lajtha LG (1977) Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol 91:335–344

    Article  CAS  PubMed  Google Scholar 

  • Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317

    Article  CAS  PubMed  Google Scholar 

  • Ducy P, Karsenty G (1995) Two distinct osteoblast-specific cis-acting elements control expression of a mouse osteocalcin gene. Mol Cell Biol 15:1858–1869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100:197–207

    Article  CAS  PubMed  Google Scholar 

  • Elkasrawy MN, Hamrick MW (2010) Myostatin (GDF-8) as a key factor linking muscle mass and bone structure. J Musculoskelet Neuronal Interact 10:56–63

    CAS  PubMed  Google Scholar 

  • Emont MP, Yu H, Wu J (2015) Transcriptional control and hormonal response of thermogenic fat. J Endocrinol 225:R35–R47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eskildsen T, Taipaleenmaki H, Stenvang J, Abdallah BM, Ditzel N, Nossent AY, Bak M, Kauppinen S, Kassem M (2011) MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo. Proc Natl Acad Sci U S A 108:6139–6144

    Article  PubMed  PubMed Central  Google Scholar 

  • Friedenstein AJ (1976) Precursor cells of mechanocytes. Int Rev Cytol 47:327–359

    Article  CAS  PubMed  Google Scholar 

  • Friedenstein AJ, Lalykina KS (1972) Thymus cells are inducible to osteogenesis. Eur J Immunol 2:602–603

    Article  CAS  PubMed  Google Scholar 

  • Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6:230–247

    Article  CAS  PubMed  Google Scholar 

  • Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3:393–403

    CAS  PubMed  Google Scholar 

  • Galipeau J, Krampera M (2015) The challenge of defining mesenchymal stromal cell potency assays and their potential use as release criteria. Cytotherapy 17:125–127

    Article  PubMed  Google Scholar 

  • Galipeau J, Krampera M, Barrett J, Dazzi F, Deans RJ, DeBruijn J, Dominici M, Fibbe WE, Gee AP, Gimble JM, Hematti P, Koh MB, LeBlanc K, Martin I, McNiece IK, Mendicino M, Oh S, Ortiz L, Phinney DG, Planat V, Shi Y, Stroncek DF, Viswanathan S, Weiss DJ, Sensebe L (2016) International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials. Cytotherapy 18:151–159

    Article  CAS  PubMed  Google Scholar 

  • 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 270:30973–30979

    Article  CAS  PubMed  Google Scholar 

  • Gimble JM (1990) The function of adipocytes in the bone marrow stroma. New Biol 2:304–312

    CAS  PubMed  Google Scholar 

  • Gimble JM, Nuttall ME (2004) Bone and fat: old questions, new insights. Endocrine 23:183–188

    Article  CAS  PubMed  Google Scholar 

  • Green H, Kehinde O (1975) An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. Cell 5:19–27

    Article  CAS  PubMed  Google Scholar 

  • Grigoriadis AE, Heersche JN, Aubin JE (1988) Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: effect of dexamethasone. J Cell Biol 106:2139–2151

    Article  CAS  PubMed  Google Scholar 

  • Hamrick MW (2017) Role of the Cytokine-like Hormone Leptin in Muscle-bone Crosstalk with Aging. J Bone Metab 24:1–8

    Article  PubMed  PubMed Central  Google Scholar 

  • Hamrick MW, Della-Fera MA, Choi YH, Pennington C, Hartzell D, Baile CA (2005) Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. J Bone Miner Res 20:994–1001

    Article  CAS  PubMed  Google Scholar 

  • Hamrick MW, Ding KH, Pennington C, Chao YJ, Wu YD, Howard B, Immel D, Borlongan C, McNeil PL, Bollag WB, Curl WW, Yu J, Isales CM (2006) Age-related loss of muscle mass and bone strength in mice is associated with a decline in physical activity and serum leptin. Bone 39:845–853

    Article  CAS  PubMed  Google Scholar 

  • Hamrick MW, McGee-Lawrence ME, Frechette DM (2016) Fatty Infiltration of Skeletal Muscle: Mechanisms and Comparisons with Bone Marrow Adiposity. Front Endocrinol (Lausanne) 7:69

    Article  Google Scholar 

  • Harms M, Seale P (2013) Brown and beige fat: development, function and therapeutic potential. Nat Med 19:1252–1263

    Article  CAS  PubMed  Google Scholar 

  • Hassan MQ, Tye CE, Stein GS, Lian JB (2015) Non-coding RNAs: Epigenetic regulators of bone development and homeostasis. Bone 81:746–756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hodges WM, O’Brien F, Fulzele S, Hamrick MW (2017) Function of microRNAs in the osteogenic differentiation and therapeutic application of adipose-derived stem cells (ASCs). Intl J Mol Sci 18:pii: E2597

    Article  CAS  Google Scholar 

  • Ilich JZ, Kelly OJ, Inglis JE, Panton LB, Duque G, Ormsbee MJ (2014) Interrelationship among muscle, fat, and bone: connecting the dots on cellular, hormonal, and whole body levels. Ageing Res Rev 15:51–60

    Article  CAS  PubMed  Google Scholar 

  • Kaji H (2016) Effects of myokines on bone. Bonekey Rep 5:826

    Article  PubMed  PubMed Central  Google Scholar 

  • Kalinkovich A, Livshits G (2017) Sarcopenic obesity or obese sarcopenia: a cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis. Ageing Res Rev 35:200–221

    Article  CAS  PubMed  Google Scholar 

  • Kim KM, Lim SK (2014) Role of miRNAs in bone and their potential as therapeutic targets. Curr Opin Pharmacol 16:133–141

    Article  PubMed  CAS  Google Scholar 

  • Kupcova Skalnikova H (2013) Proteomic techniques for characterisation of mesenchymal stem cell secretome. Biochimie 95:2196–2211

    Article  CAS  PubMed  Google Scholar 

  • Langer R, Vacanti JP (1993) Tissue engineering. Science 260:920–926

    Article  CAS  PubMed  Google Scholar 

  • Lanotte M, Scott D, Dexter TM, Allen TD (1982) Clonal preadipocyte cell lines with different phenotypes derived from murine marrow stroma: factors influencing growth and adipogenesis in vitro. J Cell Physiol 111:177–186

    Article  CAS  PubMed  Google Scholar 

  • Lassar AB, Paterson BM, Weintraub H (1986) Transfection of a DNA locus that mediates the conversion of 10T1/2 fibroblasts to myoblasts. Cell 47:649–656

    Article  CAS  PubMed  Google Scholar 

  • Li B (2018) MicroRNA Regulation in Osteogenic and Adipogenic Differentiation of Bone Mesenchymal Stem Cells and its Application in Bone Regeneration. Curr Stem Cell Res Ther 13:26–30

    CAS  PubMed  Google Scholar 

  • Ma Y, Li X, Zhang H, Ou Y, Zhang Z, Li S, Wu F, Sheng Z, Liao E (2016) Serum myostatin in central south Chinese postmenopausal women: Relationship with body composition, lipids and bone mineral density. Endocr Res 41:223–228

    Article  CAS  PubMed  Google Scholar 

  • Martin EC, Qureshi AT, Dasa V, Freitas MA, Gimble JM, Davis TA (2016) MicroRNA regulation of stem cell differentiation and diseases of the bone and adipose tissue: Perspectives on miRNA biogenesis and cellular transcriptome. Biochimie 124:98–111

    Article  CAS  PubMed  Google Scholar 

  • Maumus M, Jorgensen C, Noel D (2013) Mesenchymal stem cells in regenerative medicine applied to rheumatic diseases: role of secretome and exosomes. Biochimie 95:2229–2234

    Article  CAS  PubMed  Google Scholar 

  • McDonnell DP, Mangelsdorf DJ, Pike JW, Haussler MR, O’Malley BW (1987) Molecular cloning of complementary DNA encoding the avian receptor for vitamin D. Science 235:1214–1217

    Article  CAS  PubMed  Google Scholar 

  • Merriman HL, van Wijnen AJ, Hiebert S, Bidwell JP, Fey E, Lian J, Stein J, Stein GS (1995) The tissue-specific nuclear matrix protein, NMP-2, is a member of the AML/CBF/PEBP2/runt domain transcription factor family: interactions with the osteocalcin gene promoter. Biochemistry 34:13125–13132

    Article  CAS  PubMed  Google Scholar 

  • Meunier P, Aaron J, Edouard C, Vignon G (1971) Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies. Clin Orthop Relat Res 80:147–154

    Article  CAS  PubMed  Google Scholar 

  • Owen M (1988) Marrow stromal stem cells. J Cell Sci Suppl 10:63–76

    Article  CAS  PubMed  Google Scholar 

  • Owen M, Friedenstein AJ (1988) Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found Symp 136:42–60

    CAS  PubMed  Google Scholar 

  • Pal China S, Sanyal S, Chattopadhyay N (2018) Adiponectin signaling and its role in bone metabolism. Cytokine 112:116–131

    Article  CAS  PubMed  Google Scholar 

  • Pandey AC, Semon JA, Kaushal D, O’Sullivan RP, Glowacki J, Gimble JM, Bunnell BA (2011) MicroRNA profiling reveals age-dependent differential expression of nuclear factor kappaB and mitogen-activated protein kinase in adipose and bone marrow-derived human mesenchymal stem cells. Stem Cell Res Ther 2:49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pedersen BK, Febbraio MA (2012) Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8:457–465

    Article  CAS  PubMed  Google Scholar 

  • Pratesi A, Tarantini F, Di Bari M (2013) Skeletal muscle: an endocrine organ. Clin Cases Miner Bone Metab 10:11–14

    PubMed  PubMed Central  Google Scholar 

  • Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92:829–839

    Article  CAS  PubMed  Google Scholar 

  • Reznikoff CA, Bertram JS, Brankow DW, Heidelberger C (1973a) Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to postconfluence inhibition of cell division. Cancer Res 33:3239–3249

    CAS  PubMed  Google Scholar 

  • Reznikoff CA, Brankow DW, Heidelberger C (1973b) Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res 33:3231–3238

    CAS  PubMed  Google Scholar 

  • Ribeiro CA, Fraga JS, Graos M, Neves NM, Reis RL, Gimble JM, Sousa N, Salgado AJ (2012) The secretome of stem cells isolated from the adipose tissue and Wharton jelly acts differently on central nervous system derived cell populations. Stem Cell Res Ther 3:18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruckle J, Jacobs M, Kramer W, Pearsall AE, Kumar R, Underwood KW, Seehra J, Yang Y, Condon CH, Sherman ML (2009) Single-dose, randomized, double-blind, placebo-controlled study of ACE-011 (ActRIIA-IgG1) in postmenopausal women. J Bone Miner Res 24:744–752

    Article  CAS  PubMed  Google Scholar 

  • Rudnicki MA, Williams BO (2015) Wnt signaling in bone and muscle. Bone 80:60–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salgado AJ, Gimble JM (2013) Secretome of mesenchymal stem/stromal cells in regenerative medicine. Biochimie 95:2195

    Article  CAS  PubMed  Google Scholar 

  • Salgado AJ, Reis RL, Sousa NJ, Gimble JM (2010) Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine. Curr Stem Cell Res Ther 5:103–110

    Article  CAS  PubMed  Google Scholar 

  • Scimeca JC, Verron E (2017) The multiple therapeutic applications of miRNAs for bone regenerative medicine. Drug Discov Today 22:1084–1091

    Article  CAS  PubMed  Google Scholar 

  • Tagliaferri C, Wittrant Y, Davicco MJ, Walrand S, Coxam V (2015) Muscle and bone, two interconnected tissues. Ageing Res Rev 21:55–70

    Article  CAS  PubMed  Google Scholar 

  • Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305–317

    Article  CAS  PubMed  Google Scholar 

  • Tapscott SJ, Davis RL, Thayer MJ, Cheng PF, Weintraub H, Lassar AB (1988) MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts. Science 242:405–411

    Article  CAS  PubMed  Google Scholar 

  • Taylor SM, Jones PA (1979) Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell 17:771–779

    Article  CAS  PubMed  Google Scholar 

  • Teixeira FG, Carvalho MM, Sousa N, Salgado AJ (2013) Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration? Cell Mol Life Sci CMLS 70:3871–3882

    Article  CAS  PubMed  Google Scholar 

  • Teixeira FG, Carvalho MM, Neves-Carvalho A, Panchalingam KM, Behie LA, Pinto L, Sousa N, Salgado AJ (2015) Secretome of mesenchymal progenitors from the umbilical cord acts as modulator of neural/glial proliferation and differentiation. Stem Cell Rev 11:288–297

    Article  CAS  Google Scholar 

  • Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM (1994) mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 8:1224–1234

    Article  CAS  PubMed  Google Scholar 

  • Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, Tran TT, Suzuki R, Espinoza DO, Yamamoto Y, Ahrens MJ, Dudley AT, Norris AW, Kulkarni RN, Kahn CR (2008) New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454:1000–1004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Umek RM, Friedman AD, McKnight SL (1991) CCAAT-enhancer binding protein: a component of a differentiation switch. Science 251:288–292

    Article  CAS  PubMed  Google Scholar 

  • van der Eerden BC (2014) MicroRNAs in the skeleton: cell-restricted or potent intercellular communicators? Arch Biochem Biophys 561:46–55

    Article  PubMed  CAS  Google Scholar 

  • Wei J, Karsenty G (2015) An overview of the metabolic functions of osteocalcin. Rev Endocr Metab Disord 16:93–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei J, Ferron M, Clarke CJ, Hannun YA, Jiang H, Blaner WS, Karsenty G (2014) Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation. J Clin Invest 124:1–13

    Article  PubMed  CAS  Google Scholar 

  • Weinberger C, Hollenberg SM, Ong ES, Harmon JM, Brower ST, Cidlowski J, Thompson EB, Rosenfeld MG, Evans RM (1985) Identification of human glucocorticoid receptor complementary DNA clones by epitope selection. Science 228:740–742

    Article  CAS  PubMed  Google Scholar 

  • Wright WE, Sassoon DA, Lin VK (1989) Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD. Cell 56:607–617

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Qu J, Li H, Yuan H, Guo Q, Ouyang Z, Lu Q (2018) Relationship between serum level of GDF8, GDF11 and bone mineral density in girls with anorexia nervosa. Clin Endocrinol 90(1):88–93

    Article  CAS  Google Scholar 

  • Yin H, Price F, Rudnicki MA (2013) Satellite cells and the muscle stem cell niche. Physiol Rev 93:23–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young HE, Ceballos EM, Smith JC, Mancini ML, Wright RP, Ragan BL, Bushell I, Lucas PA (1993) Pluripotent mesenchymal stem cells reside within avian connective tissue matrices. In Vitro Cell Dev Biol Anim 29A:723–736

    Article  CAS  PubMed  Google Scholar 

  • Zaragosi LE, Wdziekonski B, Villageois P, Keophiphath M, Maumus M, Tchkonia T, Bourlier V, Mohsen-Kanson T, Ladoux A, Elabd C, Scheideler M, Trajanoski Z, Takashima Y, Amri EZ, Lacasa D, Sengenes C, Ailhaud G, Clement K, Bouloumie A, Kirkland JL, Dani C (2010) Activin a plays a critical role in proliferation and differentiation of human adipose progenitors. Diabetes 59:2513–2521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zvonic S, Lefevre M, Kilroy G, Floyd ZE, DeLany JP, Kheterpal I, Gravois A, Dow R, White A, Wu X, Gimble JM (2007) Secretome of primary cultures of human adipose-derived stem cells: modulation of serpins by adipogenesis. Mol Cell Proteom MCP 6:18–28

    Article  CAS  Google Scholar 

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Acknowledgements and Disclosures

The author wishes to thank Ms. Andrea Alarcon and Dr. Xiying Wu (LaCell LLC) and Dr. Trivia Frazier (Obatala Sciences) for their discussion and critical review of this manuscript during its preparation. The author is the co-owner, co-founder, and Chief Scientific Officer of LaCell LLC, a for profit biotechnology company focusing on stromal/stem cell therapies and investigation and the co-owner and co-founder of Obatala Sciences, Inc., a fat on a chip discovery company, and Talaria Antibodies Inc., a custom antibody production company.

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  1. LaCell LLC, New Orleans, LA, USA

    Jeffrey M. Gimble

  2. Center for Stem Cell Research & Regenerative Medicine and Departments of Medicine, Structural and Cell Biology, and Surgery, Tulane University School of Medicine, New Orleans, LA, USA

    Jeffrey M. Gimble

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Correspondence to Jeffrey M. Gimble .

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  1. Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St. Albans, VIC, Australia, Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, VIC, Australia

    Gustavo Duque

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Gimble, J.M. (2019). Mesenchymal Stem Cells as Regulators of Bone, Muscle, and Fat Formation. In: Duque, G. (eds) Osteosarcopenia: Bone, Muscle and Fat Interactions. Springer, Cham. https://doi.org/10.1007/978-3-030-25890-0_2

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