Gerbaix Maude, Vico Laurence, Ferrari Serge L, Bonnet Nicolas
Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva 14, Switzerland.
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.
Bone. 2015 Feb;71:94-100. doi: 10.1016/j.bone.2014.10.011. Epub 2014 Oct 23.
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).
骨膜蛋白（Postn基因的产物）是一种基质细胞蛋白，在机械刺激下，骨膜成骨细胞和骨细胞中其表达会增加。我们之前报道过，骨膜蛋白缺陷小鼠（Postn(-/-)）由于缺乏机械负荷对硬化蛋白（Sost基因的产物）的抑制作用，导致骨量较低且对体力活动的反应减弱。在此，我们假设骨膜蛋白在控制后肢悬吊（HU）诱导的卸载过程中的骨质流失中可能起核心作用。在Postn(+/+)小鼠（野生型同窝小鼠）中，HU显著降低了股骨骨密度以及小梁骨体积分数（BV/TV）和厚度（Tb.Th）。股骨中轴的皮质骨体积和厚度也显著降低。这些变化可通过内皮质和骨膜骨形成活性的抑制来解释，并且与HU后早期Postn表达的降低以及Sost的连续增加相关。虽然Postn(-/-)小鼠的小梁骨丢失与Postn(+/+)小鼠相当，但HU并未显著改变Postn(-/-)小鼠的皮质骨微观结构和强度。这些小鼠的骨形成保持不变，因为在缺乏骨膜蛋白的情况下Sost并未增加。相反，HU引起的Dkk1、Rankl和Opg表达变化与Postn(+/+)小鼠相似，表明骨膜蛋白表达的变化与Sost的变化非常特异性相关。总之，HU抑制骨膜蛋白表达，而骨膜蛋白表达反过来通过增加Sost在皮质骨丢失中起重要作用。这些结果进一步表明骨膜蛋白是皮质骨对机械力（加载和卸载）反应的重要介质。
