title: The matricellular protein periostin is required for sost inhibition and the anabolic response to mechanical loading and physical activity.
abstract: Periostin (gene Postn) is a secreted extracellular matrix protein involved in cell recruitment and adhesion and plays an important role in odontogenesis. In bone, periostin is preferentially expressed in the periosteum, but its functional significance remains unclear. We investigated Postn(-/-) mice and their wild type littermates to elucidate the role of periostin in the skeletal response to moderate physical activity and direct axial compression of the tibia. Furthermore, we administered a sclerostin-blocking antibody to these mice in order to demonstrate the influence of sustained Sost expression in their altered bone phenotypes. Cancellous and cortical bone microarchitecture as well as bending strength were altered in Postn(-/-) compared with Postn(+/+) mice. Exercise and axial compression both significantly increased bone mineral density and trabecular and cortical microarchitecture as well as biomechanical properties of the long bones in Postn(+/+) mice by increasing the bone formation activity, particularly at the periosteum. These changes correlated with an increase of periostin expression and a consecutive decrease of Sost in the stimulated bones. In contrast, mechanical stimuli had no effect on the skeletal properties of Postn(-/-) mice, where base-line expression of Sost levels were higher than Postn(+/+) and remained unchanged following axial compression. In turn, the concomitant injection of sclerostin-blocking antibody rescued the bone biomechanical response in Postn(-/-) mice. Taken together, these results indicate that the matricellular periostin protein is required for Sost inhibition and thereby plays an important role in the determination of bone mass and microstructural in response to loading.
authors.affiliation: Division of Bone Diseases, Department of Rehabilitation and Geriatrics, World Health Organization Collaborating Center for Osteoporosis Prevention, 1211 Geneva 14, Switzerland. Nicolas.bonnet@unige.ch
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bonnet
authors.forename: Kara N
authors.initials: KN
authors.lastname: Standley
authors.forename: Estelle N
authors.initials: EN
authors.lastname: Bianchi
authors.forename: Vincent
authors.initials: V
authors.lastname: Stadelmann
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Foti
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.forename: Serge L
authors.initials: SL
authors.lastname: Ferrari
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015519:Bone Density / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D005819:Genetic Markers / Q000235:genetics; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000502:physiology*; D010521:Periosteum / Q000166:cytology / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D013977:Tibia / Q000166:cytology / Q000378:metabolism*; D016474:Weight-Bearing
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D005819:Genetic Markers; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C082838:Postn protein, mouse; C486030:Sost protein, mouse