Energy metabolism in osteoclast formation and activity. (October 2016)

• Record Type: Journal Article
• Authors: Lemma, Silvia; Sboarina, Martina; Porporato, Paolo E.; Zini, Nicoletta; Sonveaux, Pierre; Di Pompo, Gemma; Baldini, Nicola; Avnet, Sofia
• Is Part Of: International journal of biochemistry & cell biology. Volume 79(2016:Oct.)
• Page Start: 168
• Page End: 180
• Publication Date: 2016-10
• Subjects: ATP adenosine triphosphate -- M-CSF macrophage colony-stimulating factor -- RANKL receptor activator of nuclear factor-kappa B ligand -- OxPhos oxidative phosphorylation -- TCA Cycle tricarboxylic acid cycle -- NF-kB nuclear factor-kappa B -- PGC-1β peroxisome proliferator-activated receptor-Γ coactivator 1β -- V-Atpases vacuolar H(+)-ATPases -- PBMC peripheral blood mononuclear cells -- TRAP tartrate-resistant acid phosphatase -- HSP60 heat shock protein 60 KDa -- GAPDH glyceraldehyde 3-phosphate dehydrogenase -- PKM2 pyruvate kinase isozymes M2 -- OCR oxygen consumption rate -- ECAR extracellular acidification rate -- FCCP carbonyl cyanide 4-trifluoromethoxy phenylhydrazone -- mtOCR mitochondrial OCR -- ROI region of interest -- mtDNA mitochondrial DNA -- PI propidium iodide; Osteoclast -- Energy metabolism -- Mitochondria -- Glycolytic efficiency -- Differentiation; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2016.08.034
• Languages: English
• ISSNs: 1357-2725

Abstract

Graphical abstract: Abstract: Osteoclastogenesis and osteolysis are energy-consuming processes supported by high metabolic activities. In human osteoclasts derived from the fusion of monocytic precursors, we found a substantial increase in the number of mitochondria with differentiation. In mature osteoclasts, mitochondria were also increased in size, rich of cristae and arranged in a complex tubular network. When compared with immature cells, fully differentiated osteoclasts showed higher levels of enzymes of the electron transport chain, a higher mitochondrial oxygen consumption rate and a lower glycolytic efficiency, as evaluated by extracellular flux analysis and by the quantification of metabolites in the culture supernatant. Thus, oxidative phosphorylation appeared the main bioenergetic source for osteoclast formation. Conversely, we found that bone resorption mainly relied on glycolysis. In fact, osteoclast fuelling with galactose, forcing cells to depend on Oxidative Phosphorylation by reducing the rate of glycolysis, significantly impaired Type I collagen degradation, whereas non-cytotoxic doses of rotenone, an inhibitor of the mitochondrial complex I, enhanced osteoclast activity. Furthermore, we found that the enzymes associated to the glycolytic pathway are localised close to the actin ring of polarised osteoclasts, where energy-demanding activities associated with bone degradation take place. In conclusion, we demonstrate that the energy required for osteoclast differentiation mainly derives from mitochondrial oxidative metabolism, whereas the peripheral cellular activities associated with bone matrix degradation are supported by glycolysis. A better understanding of human osteoclast energy metabolism holds the potential for future therapeutic interventions aimed to target osteoclast activity in different pathological conditions of bone.