title: Effects of chronic hypergravity: from adaptive to deleterious responses in growing mouse skeleton.
abstract: One of the most important but least studied environmental factors playing a major role in bone physiology is gravity. While the knowledge of deleterious effects of microgravity on the skeleton is expanding, little is known about hypergravity and its osteogenic potential. Centrifugation was used to assess effects of 21-day continuous 2- or 3-g acceleration on femur and L2-vertebra of 7-wk-old male C57BL/6 mice. Under 3 g, body mass growth slowed down, and deleterious skeletal effects were found (P < 0.05 compared with control): cortical thinning, osteoclasts surface increase (+41% in femur, +20% in vertebra), and bone formation rate decrease (-34% in femur, -38% in vertebra). A 2-g centrifugation did not reduce body mass and improved trabecular volume (+18% in femur, +13% in vertebra) and microarchitecture (+32% connectivity density in femur, +9% trabecular thickness in vertebra, P < 0.05 compared with control). Centrifugation at 2 g also decreased osteoclast surfaces (-36% in femur, -16% in vertebra) and increased the extent of mineralized surfaces (+31% in femur, +48% in vertebra, P < 0.05 compare to control). Quantitative immunohistochemistry revealed an increase of dentin matrix acidic phosphoprotein 1 (DMP1) and decrease of sclerostin (+60% and -35% respectively, P < 0.001 compared with control) in the femur cortex of 2-g mice. In the distal femur metaphysis, the number and volume of blood vessels increased by 22 and 44%, respectively (P < 0.05 compared with control). In conclusion, the effects of continuous hypergravity were bone compartment-specific and depended on the gravity level, with a threshold between beneficial 2-g and deleterious 3-g effects.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France.
authors.forename: Vasily
authors.initials: V
authors.lastname: Gnyubkin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Guignandon
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Laroche
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Vanden-Bossche
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Normand
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Lafage-Proust
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1059, laboratoire de Biologie intégrative du Tissu Osseux, Université de Lyon, Saint-Etienne, France vico@univ-st-etienne.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Vico
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D015519:Bone Density / Q000502:physiology*; D001846:Bone Development / Q000502:physiology*; D005269:Femur / Q000254:growth & development*; D018471:Hypergravity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
keywords: DMP1; bone vascularization; immunohistochemistry; microcomputed tomography; osteocytes; sclerostin