Format

Send to

Choose Destination
J Bone Miner Res. 2018 Jun;33(6):1052-1065. doi: 10.1002/jbmr.3390. Epub 2018 Mar 30.

Osteoblast-like MC3T3-E1 Cells Prefer Glycolysis for ATP Production but Adipocyte-like 3T3-L1 Cells Prefer Oxidative Phosphorylation.

Author information

1
Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, ME, USA.
2
Department of Biological and Pharmaceutical Sciences, Touro University California College of Pharmacy, Vallejo, CA, USA.
3
Buck Institute for Research on Aging, Novato, CA, USA.
4
Harvard School of Dental Medicine, Boston, MA, USA.
5
University of North Carolina, Chapel Hill, NC, USA.

Abstract

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.

KEYWORDS:

ADIPOCYTE; EXTRACELLULAR FLUX ANALYSIS; GLYCOLYSIS; OSTEOBLAST; OXIDATIVE PHOSPHORYLATION

PMID:
29342317
PMCID:
PMC6002892
[Available on 2019-06-01]
DOI:
10.1002/jbmr.3390

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center