PMID- 33307974
OWN - NLM
STAT- MEDLINE
DCOM- 20211213
LR  - 20220202
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Print)
IS  - 1547-3287 (Linking)
VI  - 30
IP  - 3
DP  - 2021 Feb
TI  - Energy Metabolism During Osteogenic Differentiation: The Role of Akt.
PG  - 149-162
LID - 10.1089/scd.2020.0141 [doi]
AB  - Osteogenic differentiation, the process by which bone marrow mesenchymal 
      stem/stromal (a.k.a. skeletal stem) cells and osteoprogenitors form osteoblasts, 
      is a critical event for bone formation during development, fracture repair, and 
      tissue maintenance. Extra cellular and intracellular signaling pathways 
      triggering osteogenic differentiation are relatively well known; however, the 
      ensuing change in cell energy metabolism is less clearly defined. We and others 
      have previously reported activation of mitochondria during osteogenic 
      differentiation. To further elucidate the involved bioenergetic mechanisms and 
      triggers, we tested the effect of osteogenic media containing ascorbate and 
      beta-glycerol phosphate, or various osteogenic hormones and growth factors on energy 
      metabolism in long bone (ST2)- and calvarial bone (MC3T3-E1)-derived 
      osteoprogenitors. We show that osteogenic media and differentiation factors, 
      Wnt3a and BMP2, stimulate mitochondrial oxidative phosphorylation (OxPhos) with 
      little effect on glycolysis. The activation of OxPhos occurs acutely, suggesting 
      a metabolic signaling change rather than protein expression change. To this end, 
      we found that the observed mitochondrial activation is Akt dependent. Akt is 
      activated by osteogenic media, Wnt3a, and BMP2, leading to increased 
      phosphorylation of various mitochondrial Akt targets, a phenomenon known to 
      stimulate OxPhos. In sum, our data provide comprehensive analysis of cellular 
      bioenergetics during osteoinduction in cells of two different origins (mesenchyme 
      vs neural crest) and identify Wnt3a and BMP2 as physiological stimulators of 
      mitochondrial respiration through Akt activation.
FAU - Smith, Charles Owen
AU  - Smith CO
AD  - Center for Musculoskeletal Research, University of Rochester School of Medicine & 
      Dentistry, Rochester, New York, USA.
FAU - Eliseev, Roman A
AU  - Eliseev RA
AD  - Center for Musculoskeletal Research, University of Rochester School of Medicine & 
      Dentistry, Rochester, New York, USA.
LA  - eng
GR  - R01 AR072601/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210111
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Wnt3A Protein)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Bone Morphogenetic Protein 2/metabolism/pharmacology
MH  - Cell Differentiation/drug effects/*physiology
MH  - Cell Line
MH  - Energy Metabolism/drug effects/*physiology
MH  - Mesenchymal Stem Cells/cytology/metabolism/physiology
MH  - Mice
MH  - Mitochondria/metabolism
MH  - Osteoblasts/cytology/metabolism/physiology
MH  - Osteogenesis/drug effects/*physiology
MH  - Oxidative Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism/*physiology
MH  - Signal Transduction/physiology
MH  - Stem Cells/cytology/metabolism/physiology
MH  - Wnt3A Protein/metabolism/pharmacology
PMC - PMC7876359
OTO - NOTNLM
OT  - Akt
OT  - BMP2
OT  - Wnt
OT  - differentiation
OT  - mitochondria
OT  - osteoblast
COIS- The authors have nothing to disclose.
EDAT- 2020/12/15 06:00
MHDA- 2021/12/15 06:00
PMCR- 2022/02/01
CRDT- 2020/12/14 09:50
PHST- 2020/12/15 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2020/12/14 09:50 [entrez]
PHST- 2022/02/01 00:00 [pmc-release]
AID - 10.1089/scd.2020.0141 [pii]
AID - 10.1089/scd.2020.0141 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2021 Feb;30(3):149-162. doi: 10.1089/scd.2020.0141. Epub 2021 Jan 
      11.