The Matricellular Protein Periostin Is Required for Sost Inhibition and the Anabolic Response to Mechanical Loading and Physical Activity
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Bonnet, Nicolas, Standley, Kara N., Bianchi, Estelle N., Stadelmann, Vincent, Foti, Michelangelo, Conway, Simon J, Ferrari, Serge L. and Kneissel, Michaela (2009) The Matricellular Protein Periostin Is Required for Sost Inhibition and the Anabolic Response to Mechanical Loading and Physical Activity. Journal of Biological Chemistry, 284 (51). pp. 35939-35950. ISSN 0021-9258
Abstract
Periostin (Postn) is an extracellular matrix protein involved in cell recruitment and adhesion and plays an important role in odontogenesis. In bone, Postn is preferentially expressed in the periosteum, but its functional significance remains unclear. We investigated Postn-/- mice and their wildtype littermates to elucidate the role of Postn in the skeletal response to moderate physical activity and direct axial compression of the tibia. Furthermore, we administered a sclerostin blocking antibody (Sost-Ab) 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 to Postn+/+ mice. Exercise and axial compression both significantly increased BMD, 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 Postn 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, which baseline expression levels of Sost were higher and remained unchanged following axial compression. In turn, the concomitant injection of Sost-Ab rescued the bone biomechanical response in Postn-/- mice.
Taken together, these results indicate that periostin is required for Sost inhibition and thereby plays an important role in the determination of bone mass and microstructure in response to loading.
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| Date Deposited: | 13 Oct 2015 13:17 |
| Last Modified: | 13 Oct 2015 13:17 |
| URI: | https://oak.novartis.com/id/eprint/1157 |