Abstract
SUMMARYThe metabolic program of osteoblasts, the chief bone-making cells, remains incompletely understood. Here in murine calvarial cells, we establish that osteoblast differentiation under aerobic conditions is coupled with a marked increase in glucose consumption and lactate production but reduced oxygen consumption. As a result, aerobic glycolysis accounts for approximately 80% of the ATP production in mature osteoblasts. In vivo tracing with 13C-labeled glucose in the mouse shows that glucose in bone is readily metabolized to lactate but not organic acids in the TCA cycle. Glucose tracing in osteoblast cultures reveals that pyruvate is carboxylated to form malate integral to the malate-aspartate shuttle. RNA sequencing (RNA-seq) identifies Me2, encoding the mitochondrial NAD-dependent isoform of malic enzyme, as being specifically upregulated during osteoblast differentiation. Knockdown of Me2 markedly reduces the glycolytic flux and impairs osteoblast proliferation and differentiation. Thus, the mitochondrial malic enzyme functionally couples the mitochondria with aerobic glycolysis in osteoblasts.
Highlights
Proper bone remodeling is essential for maintaining the integrity of bone, and it requires an exquisite balance between bone resorption by osteoclasts and bone formation by osteoblasts
We show that aerobic glycolysis is a main bioenergetic mechanism throughout differentiation and especially dominates energy production in mature osteoblasts
We further demonstrate that the malate-aspartate shuttle between mitochondria and the cytosol is necessary for active glycolysis in the osteoblast
Summary
Proper bone remodeling is essential for maintaining the integrity of bone, and it requires an exquisite balance between bone resorption by osteoclasts and bone formation by osteoblasts. The bone anabolic function of PTH and Wnt signaling has been partially attributed to their regulation of osteoblast metabolism (Chen et al, 2019; Esen et al, 2013, 2015; Frey et al, 2015; Karner et al, 2015). These advances have raised the potential that metabolic pathways may be targeted for developing additional bone therapies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
