title: Anaplerotic Accumulation of Tricarboxylic Acid Cycle Intermediates as Well as Changes in Other Key Metabolites During Heterotopic Ossification.
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.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, 77030.
authors.forename: Eleanor L
authors.initials: EL
authors.lastname: Davis
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, 77030.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Salisbury
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, 77030.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 77030.|Department of Orthopedic Surgery, Baylor College of Medicine, Houston, Texas, 77030.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Olmsted-Davis
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, 77030.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 77030.|Department of Orthopedic Surgery, Baylor College of Medicine, Houston, Texas, 77030.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Davis
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D002952:Citric Acid Cycle / Q000235:genetics*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D007273:Injections, Intramuscular; D055442:Metabolome; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009999:Ossification, Heterotopic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2
keywords: BMP2; METABOLOMICS; TRANSIENT BROWN FAT; TRICARBOXYLIC ACID CYCLE