title: Energy metabolism in osteoclast formation and activity.
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.
authors: Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli (IOR), via di Barbiano 1/10, 40136 Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, 40136 Bologna, Italy.
authors: Silvia
authors: S
authors: Lemma
authors: Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School, Brussels 1200, Belgium.
authors: Martina
authors: M
authors: Sboarina
authors: Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School, Brussels 1200, Belgium.
authors: Paolo E
authors: PE
authors: Porporato
authors: CNR - National Research Council of Italy, Institute of Molecular Genetics, 40136 Bologna, Italy; Laboratory of Musculoskeletal Cell Biology, Istituto Ortopedico Rizzoli (IOR), 40136 Bologna, Italy.
authors: Nicoletta
authors: N
authors: Zini
authors: Pole of Pharmacology, Institute of Experimental and Clinical Research (IREC), Université catholique de Louvain (UCL) Medical School, Brussels 1200, Belgium.
authors: Pierre
authors: P
authors: Sonveaux
authors: Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli (IOR), via di Barbiano 1/10, 40136 Bologna, Italy.
authors: Gemma
authors: G
authors: Di Pompo
authors: Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli (IOR), via di Barbiano 1/10, 40136 Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, 40136 Bologna, Italy.
authors: Nicola
authors: N
authors: Baldini
authors: Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli (IOR), via di Barbiano 1/10, 40136 Bologna, Italy. Electronic address: sofia.avnet@ior.it.
authors: Sofia
authors: S
authors: Avnet
mesh_terms: D002454:Cell Differentiation; D024042:Collagen Type I / Q000378:metabolism; D004734:Energy Metabolism; D006019:Glycolysis; D006801:Humans; D053142:Mitochondrial Size; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*
chemical_list: D024042:Collagen Type I
keywords: Differentiation; Energy metabolism; Glycolytic efficiency; Mitochondria; Osteoclast