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Osteoblast‐like MC3T3‐E1 Cells Prefer Glycolysis for ATP Production but Adipocyte‐like 3T3‐L1 Cells Prefer Oxidative Phosphorylation
Author(s) -
Guntur Anyonya R,
Gerencser Akos A,
Le Phuong T,
DeMambro Victoria E,
Bornstein Sheila A,
Mookerjee Shona A,
Maridas David E,
Clemmons David E,
Brand Martin D,
Rosen Clifford J
Publication year - 2018
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3390
Subject(s) - oxidative phosphorylation , microbiology and biotechnology , mesenchymal stem cell , glycolysis , osteoblast , bioenergetics , cellular differentiation , biology , phosphorylation , adipocyte , stromal cell , chemistry , endocrinology , medicine , mitochondrion , biochemistry , adipose tissue , metabolism , cancer research , in vitro , gene
Mesenchymal stromal cells (MSCs) are early progenitors that can differentiate into osteoblasts, chondrocytes, and adipocytes. We hypothesized that osteoblasts and adipocytes utilize distinct bioenergetic pathways during MSC differentiation. To test this hypothesis, we compared the bioenergetic profiles of preosteoblast MC3T3‐E1 cells and calvarial osteoblasts with preadipocyte 3T3L1 cells, before and after differentiation. Differentiated MC3T3‐E1 osteoblasts met adenosine triphosphate (ATP) demand mainly by glycolysis with minimal reserve glycolytic capacity, whereas nondifferentiated cells generated ATP through oxidative phosphorylation. A marked Crabtree effect (acute suppression of respiration by addition of glucose, observed in both MC3T3‐E1 and calvarial osteoblasts) and smaller mitochondrial membrane potential in the differentiated osteoblasts, particularly those incubated at high glucose concentrations, indicated a suppression of oxidative phosphorylation compared with nondifferentiated osteoblasts. In contrast, both nondifferentiated and differentiated 3T3‐L1 adipocytes met ATP demand primarily by oxidative phosphorylation despite a large unused reserve glycolytic capacity. In sum, we show that nondifferentiated precursor cells prefer to use oxidative phosphorylation to generate ATP; when they differentiate to osteoblasts, they gain a strong preference for glycolytic ATP generation, but when they differentiate to adipocytes, they retain the strong preference for oxidative phosphorylation. Unique metabolic programming in mesenchymal progenitor cells may influence cell fate and ultimately determine the degree of bone formation and/or the development of marrow adiposity. © 2018 American Society for Bone and Mineral Research.