Metabolic programming determines the lineage-differentiation fate of murine bone marrow stromal progenitor cells

Michaela Tencerova*, Elizabeth Rendina-Ruedy, Ditte Neess, Nils Færgeman, Florence Figeac, Dalia Ali, Morten Danielsen, Anders Haakonsson, Clifford J. Rosen, Moustapha Kassem

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Resumé

Enhanced bone marrow adipogenesis and impaired osteoblastogenesis have been observed in obesity, suggesting that the metabolic microenvironment regulates bone marrow adipocyte and osteoblast progenitor differentiation fate. To determine the molecular mechanisms, we studied two immortalized murine cell lines of adipocyte or osteoblast progenitors (BMSCsadipo and BMSCsosteo, respectively) under basal and adipogenic culture conditions. At baseline, BMSCsadipo, and BMSCsosteo exhibit a distinct metabolic program evidenced by the presence of specific global gene expression, cellular bioenergetics, and metabolomic signatures that are dependent on insulin signaling and glycolysis in BMSCsosteo versus oxidative phosphorylation in BMSCsadipo. To test the flexibility of the metabolic program, we treated BMSCsadipo with parathyroid hormone, S961 (an inhibitor of insulin signaling) and oligomycin (an inhibitor of oxidative phosphorylation). The treatment induced significant changes in cellular bioenergetics that were associated with decreased adipocytic differentiation. Similarly, 12 weeks of a high-fat diet in mice led to the expansion of adipocyte progenitors, enhanced adipocyte differentiation and insulin signaling in cultured BMSCs. Our data demonstrate that BMSC progenitors possess a distinct metabolic program and are poised to respond to exogenous metabolic cues that regulate their differentiation fate.

OriginalsprogEngelsk
Artikelnummer35
TidsskriftBone Research
Vol/bind7
Antal sider14
ISSN2095-4700
DOI
StatusUdgivet - 1. dec. 2019

Fingeraftryk

Mesenchymal Stromal Cells
Adipocytes
Oxidative Phosphorylation
Insulin
Osteoblasts
Energy Metabolism
Adipogenesis
High Fat Diet
Glycolysis
Parathyroid Hormone
Cues
Cell Line

Citer dette

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title = "Metabolic programming determines the lineage-differentiation fate of murine bone marrow stromal progenitor cells",
abstract = "Enhanced bone marrow adipogenesis and impaired osteoblastogenesis have been observed in obesity, suggesting that the metabolic microenvironment regulates bone marrow adipocyte and osteoblast progenitor differentiation fate. To determine the molecular mechanisms, we studied two immortalized murine cell lines of adipocyte or osteoblast progenitors (BMSCsadipo and BMSCsosteo, respectively) under basal and adipogenic culture conditions. At baseline, BMSCsadipo, and BMSCsosteo exhibit a distinct metabolic program evidenced by the presence of specific global gene expression, cellular bioenergetics, and metabolomic signatures that are dependent on insulin signaling and glycolysis in BMSCsosteo versus oxidative phosphorylation in BMSCsadipo. To test the flexibility of the metabolic program, we treated BMSCsadipo with parathyroid hormone, S961 (an inhibitor of insulin signaling) and oligomycin (an inhibitor of oxidative phosphorylation). The treatment induced significant changes in cellular bioenergetics that were associated with decreased adipocytic differentiation. Similarly, 12 weeks of a high-fat diet in mice led to the expansion of adipocyte progenitors, enhanced adipocyte differentiation and insulin signaling in cultured BMSCs. Our data demonstrate that BMSC progenitors possess a distinct metabolic program and are poised to respond to exogenous metabolic cues that regulate their differentiation fate.",
author = "Michaela Tencerova and Elizabeth Rendina-Ruedy and Ditte Neess and Nils F{\ae}rgeman and Florence Figeac and Dalia Ali and Morten Danielsen and Anders Haakonsson and Rosen, {Clifford J.} and Moustapha Kassem",
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Metabolic programming determines the lineage-differentiation fate of murine bone marrow stromal progenitor cells. / Tencerova, Michaela; Rendina-Ruedy, Elizabeth; Neess, Ditte; Færgeman, Nils; Figeac, Florence; Ali, Dalia; Danielsen, Morten; Haakonsson, Anders; Rosen, Clifford J.; Kassem, Moustapha.

I: Bone Research, Bind 7, 35, 01.12.2019.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Metabolic programming determines the lineage-differentiation fate of murine bone marrow stromal progenitor cells

AU - Tencerova, Michaela

AU - Rendina-Ruedy, Elizabeth

AU - Neess, Ditte

AU - Færgeman, Nils

AU - Figeac, Florence

AU - Ali, Dalia

AU - Danielsen, Morten

AU - Haakonsson, Anders

AU - Rosen, Clifford J.

AU - Kassem, Moustapha

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Enhanced bone marrow adipogenesis and impaired osteoblastogenesis have been observed in obesity, suggesting that the metabolic microenvironment regulates bone marrow adipocyte and osteoblast progenitor differentiation fate. To determine the molecular mechanisms, we studied two immortalized murine cell lines of adipocyte or osteoblast progenitors (BMSCsadipo and BMSCsosteo, respectively) under basal and adipogenic culture conditions. At baseline, BMSCsadipo, and BMSCsosteo exhibit a distinct metabolic program evidenced by the presence of specific global gene expression, cellular bioenergetics, and metabolomic signatures that are dependent on insulin signaling and glycolysis in BMSCsosteo versus oxidative phosphorylation in BMSCsadipo. To test the flexibility of the metabolic program, we treated BMSCsadipo with parathyroid hormone, S961 (an inhibitor of insulin signaling) and oligomycin (an inhibitor of oxidative phosphorylation). The treatment induced significant changes in cellular bioenergetics that were associated with decreased adipocytic differentiation. Similarly, 12 weeks of a high-fat diet in mice led to the expansion of adipocyte progenitors, enhanced adipocyte differentiation and insulin signaling in cultured BMSCs. Our data demonstrate that BMSC progenitors possess a distinct metabolic program and are poised to respond to exogenous metabolic cues that regulate their differentiation fate.

AB - Enhanced bone marrow adipogenesis and impaired osteoblastogenesis have been observed in obesity, suggesting that the metabolic microenvironment regulates bone marrow adipocyte and osteoblast progenitor differentiation fate. To determine the molecular mechanisms, we studied two immortalized murine cell lines of adipocyte or osteoblast progenitors (BMSCsadipo and BMSCsosteo, respectively) under basal and adipogenic culture conditions. At baseline, BMSCsadipo, and BMSCsosteo exhibit a distinct metabolic program evidenced by the presence of specific global gene expression, cellular bioenergetics, and metabolomic signatures that are dependent on insulin signaling and glycolysis in BMSCsosteo versus oxidative phosphorylation in BMSCsadipo. To test the flexibility of the metabolic program, we treated BMSCsadipo with parathyroid hormone, S961 (an inhibitor of insulin signaling) and oligomycin (an inhibitor of oxidative phosphorylation). The treatment induced significant changes in cellular bioenergetics that were associated with decreased adipocytic differentiation. Similarly, 12 weeks of a high-fat diet in mice led to the expansion of adipocyte progenitors, enhanced adipocyte differentiation and insulin signaling in cultured BMSCs. Our data demonstrate that BMSC progenitors possess a distinct metabolic program and are poised to respond to exogenous metabolic cues that regulate their differentiation fate.

U2 - 10.1038/s41413-019-0076-5

DO - 10.1038/s41413-019-0076-5

M3 - Journal article

C2 - 31754546

AN - SCOPUS:85075077580

VL - 7

JO - Bone Research

JF - Bone Research

SN - 2095-4700

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ER -