Active mitochondria support osteogenic differentiation by stimulating β-catenin acetylation

The Journal of Biological Chemistry
Brianna H SharesRoman A Eliseev

Abstract

Bone marrow stromal (a.k.a. mesenchymal stem) cells (BMSCs) can differentiate into osteoblasts (OBs), adipocytes, or chondrocytes. As BMSCs undergo OB differentiation, they up-regulate mitochondrial oxidative phosphorylation (OxPhos). Here, we investigated the mechanism(s) connecting mitochondrial OxPhos to OB differentiation. First, we found that treating BMSC-like C3H10T1/2 cells with an OxPhos inhibitor reduces their osteogenic potential. Interestingly, ATP levels were not reduced, as glycolysis compensated for the decreased OxPhos. Thus, mitochondria support OB differentiation not only by supplying ATP, but also by other mechanisms. To uncover these mechanisms, we stimulated OxPhos in C3H10T1/2 cells by replacing media glucose with galactose and observed that this substitution increases both OxPhos and osteogenesis even in the absence of osteoinducers. β-Catenin, an important signaling pathway in osteogenesis, was found to be responsive to OxPhos stimulation. β-Catenin activity is maintained by acetylation, and mitochondria generate the acetyl donor acetyl-CoA, which upon entering the Krebs cycle is converted to citrate capable of exiting mitochondria. Cytosolic citrate is converted back to acetyl-CoA by ATP citrate lyase (...Continue Reading

References

Feb 15, 2001·Oncogene·A Raouf, A Seth
Apr 26, 2002·The Journal of Biological Chemistry·Daniel WolfTony Kouzarides
Apr 3, 2004·Molecular and Cellular Biology·Laurence LévyChristine Neuveut
Apr 15, 2006·The Journal of Biological Chemistry·Eun-Joo JeonSuk-Chul Bae
Mar 12, 2008·Archives of Biochemistry and Biophysics·Pierre J Marie
Oct 21, 2009·Tissue Engineering. Part C, Methods·Mika PietiläPetri Lehenkari
Apr 16, 2010·Annals of the New York Academy of Sciences·Chao WanThomas L Clemens
Jun 10, 2010·International Journal of Ayurveda Research·Prashant Kadam, Supriya Bhalerao
Nov 16, 2012·Nature·Scott B Vafai, Vamsi K Mootha
Jan 1, 2013·Molecular Cell·Ana Chocarro-CalvoCustodia García-Jiménez
Mar 7, 2014·Cell & Bioscience·Chenxi GaoJing Hu
Mar 12, 2015·Development·Paolo Bianco, Pamela G Robey
Jun 23, 2015·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Beata Lecka-Czernik, Clifford J Rosen
Oct 22, 2015·Stem Cells and Development·Laura C ShumRoman A Eliseev
Dec 8, 2015·Stem Cells·Maria Fernanda ForniAlicia J Kowaltowski
Apr 30, 2016·The Journal of Biological Chemistry·Courtney M KarnerFanxin Long
May 7, 2016·Trends in Molecular Medicine·Catherine CherryJosephine Hoh
Dec 31, 2016·International Journal of Molecular Sciences·Maria Teresa ValentiMonica Mottes
Jun 8, 2017·Journal of Cellular Physiology·Maryam MajidiniaBahman Yousefi
Aug 28, 2017·Bone·Courtney M Karner, Fanxin Long
Jan 2, 2018·Trends in Endocrinology and Metabolism : TEM·Julia LoefflerAnke Dienelt

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Citations

Jul 31, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Alex M HollenbergRoman A Eliseev
Apr 17, 2020·Frontiers in Bioengineering and Biotechnology·Þóra SigmarsdóttirÓlafur E Sigurjónsson
Jun 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Poh-Shiow YehRuei-Ming Chen
Oct 20, 2020·Frontiers in Endocrinology·Nathalie S AlekosRyan C Riddle
Nov 10, 2020·PloS One·Laura C ShumRoman A Eliseev
Jan 27, 2020·Seminars in Cancer Biology·Nicoletta UrbanoOrazio Schillaci
Dec 15, 2020·Stem Cells and Development·Charles Owen Smith, Roman A Eliseev
Nov 22, 2020·Bone·Austin P Hensley, Audrey McAlinden
Feb 2, 2021·Frontiers in Bioengineering and Biotechnology·Adelheid WeidingerAsmita Banerjee
Jan 6, 2021·Nature Metabolism·Nick van Gastel, Geert Carmeliet
Jan 24, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Kelly AscençãoCsaba Szabo
Feb 20, 2021·Molecular Genetics and Metabolism·Steven F DobrowolskiHarry C Blair
Apr 1, 2021·Life Sciences·Sulagna Mukherjee, Jong Won Yun
Apr 17, 2021·Scientific Reports·Anna V GoropashnayaVadim B Fedorov
May 1, 2021·International Journal of Molecular Sciences·Antonia DonatJohannes Keller
Jul 31, 2021·Stem Cells International·Qinglu TianYachuan Zhou
Aug 18, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Dun NiuZhizhong Xie
Nov 18, 2021·Journal of Cellular and Molecular Medicine·Xumin LiGang Wu
Nov 20, 2021·Journal of Dental Research·W CaiY Zhang

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