title: Periostin expression contributes to cortical bone loss during unloading.
abstract: Periostin (a product of Postn gene) is a matricellular protein which is increased in periosteal osteoblasts and osteocytes upon mechanical stimulation. We previously reported that periostin-deficient mice (Postn(-/-)) have low bone mass and a diminished response to physical activity due to a lack of sclerostin (a product of Sost gene) inhibition by mechanical loading. Here we hypothesized that periostin could play a central role in the control of bone loss during unloading induced by hindlimb suspension (HU). In Postn(+/+) mice (wildtype littermate), HU significantly decreased femur BMD, as well as trabecular BV/TV and thickness (Tb.Th). Cortical bone volume and thickness at the femoral midshaft, also significantly decreased. These changes were explained by an inhibition of endocortical and periosteal bone formation activity and correlated with a decrease of Postn expression and a consecutive increase in Sost early after HU. Whereas trabecular bone loss in Postn(-/-) mice was comparable to Postn(+/+) mice, HU did not significantly alter cortical bone microstructure and strength in Postn(-/-) mice. Bone formation remained unchanged in these mice, as Sost did not increase in the absence of periostin. In contrast, changes in Dkk1, Rankl and Opg expression in response to HU were similar to Postn(+/+) mice, indicating that changes in periostin expression were quite specifically related to changes in Sost. In conclusion, HU inhibits periostin expression, which in turn plays an important role in cortical bone loss through an increase in Sost. These results further indicate that periostin is an essential mediator of cortical bone response to mechanical forces (loading and unloading).
authors.affiliation: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva 14, Switzerland.
authors.forename: Maude
authors.initials: M
authors.lastname: Gerbaix
authors.affiliation: Institute National de la Santé et de la Recherche Médicale (INSERM), Unité 1059, Laboratoire de Biologie Intégrée du Tissu Osseux, Université de Lyon, St-Etienne, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Vico
authors.affiliation: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva 14, Switzerland.
authors.forename: Serge L
authors.initials: SL
authors.lastname: Ferrari
authors.affiliation: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva 14, Switzerland. Electronic address: nicolas.bonnet@unige.ch.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bonnet
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001835:Body Weight; D015519:Bone Density; D016723:Bone Remodeling; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000378:metabolism*; D002452:Cell Count; D005269:Femur / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D019417:Hindlimb Suspension; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D013131:Spine / Q000473:pathology / Q000503:physiopathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C082838:Postn protein, mouse; C486030:Sost protein, mouse
keywords: Bone formation; Cortical; Periostin; Sclerostin; Unloading