title: PTH Promotes Bone Anabolism by Stimulating Aerobic Glycolysis via IGF Signaling.
abstract: Teriparatide, a recombinant peptide corresponding to amino acids 1-34 of human parathyroid hormone (PTH), has been an effective bone anabolic drug for over a decade. However, the mechanism whereby PTH stimulates bone formation remains incompletely understood. Here we report that in cultures of osteoblast-lineage cells, PTH stimulates glucose consumption and lactate production in the presence of oxygen, a hallmark of aerobic glycolysis, also known as Warburg effect. Experiments with radioactively labeled glucose demonstrate that PTH suppresses glucose entry into the tricarboxylic acid cycle (TCA cycle). Mechanistically, the increase in aerobic glycolysis is secondary to insulin-like growth factor (Igf) signaling induced by PTH, whereas the metabolic effect of Igf is dependent on activation of mammalian target of rapamycin complex 2 (mTORC2). Importantly, pharmacological perturbation of glycolysis suppresses the bone anabolic effect of intermittent PTH in the mouse. Thus, stimulation of aerobic glycolysis via Igf signaling contributes to bone anabolism in response to PTH.
authors.affiliation: Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, USA.|Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Emel
authors.initials: E
authors.lastname: Esen
authors.affiliation: Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Seung-Yon
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Burton M
authors.initials: BM
authors.lastname: Wice
authors.affiliation: Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, USA.|Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.|Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.|Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Fanxin
authors.initials: F
authors.lastname: Long
mesh_terms: D000332:Aerobiosis / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D017874:Immediate-Early Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D000076225:Mechanistic Target of Rapamycin Complex 2; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects; D055114:X-Ray Microtomography; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D002245:Carbon Dioxide; D002247:Carbon Isotopes; D000242:Cyclic AMP; D005947:Glucose; D017874:Immediate-Early Proteins; D007334:Insulin-Like Growth Factor I; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes; D010281:Parathyroid Hormone; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases
keywords: AEROBIC GLYCOLYSIS; BONE ANABOLISM; IGF; PARATHYROID HORMONE; PTH