Anaplerotic Accumulation of Tricarboxylic Acid Cycle Intermediates as Well as Changes in Other Key Metabolites during Heterotopic Ossification

Eleanor L. Davis, Elizabeth Salisbury, Elizabeth Olmsted-Davis, Alan R. Davis

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Heterotopic ossification (HO) is the de novo formation of bone that occurs in soft tissue, through recruitment, expansion, and differentiation of multiple cells types including transient brown adipocytes, osteoblasts, chondrocytes, mast cells, and platelets to name a few. Much evidence is accumulating that suggests changes in metabolism may be required to accomplish this bone formation. Recent work using a mouse model of heterotopic bone formation reliant on delivery of adenovirus-transduced cells expressing low levels of BMP2 showed the immediate expansion of a unique brown adipocyte-like cell. These cells are undergoing robust uncoupled oxidative phosphorylation to a level such that oxygen in the microenvironment is dramatically lowered creating areas of hypoxia. It is unclear how these oxygen changes ultimately affect metabolism and bone formation. To identify the processes and changes occurring over the course of bone formation, HO was established in the mice, and tissues isolated at early and late times were subjected to a global metabolomic screen. Results show that there are significant changes in both glucose levels, as well as TCA cycle intermediates. Additionally, metabolites necessary for oxidation of stored lipids were also found to be significantly elevated. The complete results of this screen are presented here, and provide a unique picture of the metabolic changes occurring during heterotopic bone formation.

Original languageEnglish (US)
Pages (from-to)1044-1053
Number of pages10
JournalJournal of Cellular Biochemistry
Volume117
Issue number4
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

Fingerprint

Heterotopic Ossification
Citric Acid Cycle
Metabolites
Osteogenesis
Bone
Brown Adipocytes
Metabolism
Cells
Tissue
Oxygen
Metabolomics
Oxidative Phosphorylation
Osteoblasts
Chondrocytes
Platelets
Adenoviridae
Mast Cells
Names
Cell Differentiation
Blood Platelets

Keywords

  • BMP2
  • METABOLOMICS
  • TRANSIENT BROWN FAT
  • TRICARBOXYLIC ACID CYCLE

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Anaplerotic Accumulation of Tricarboxylic Acid Cycle Intermediates as Well as Changes in Other Key Metabolites during Heterotopic Ossification. / Davis, Eleanor L.; Salisbury, Elizabeth; Olmsted-Davis, Elizabeth; Davis, Alan R.

In: Journal of Cellular Biochemistry, Vol. 117, No. 4, 01.04.2016, p. 1044-1053.

Research output: Contribution to journalArticle

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