Department of Oral Cell Biology, ACTA-VU University Amsterdam, Research Institute MOVE, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, The Netherlands.
Odontology. 2011 Jul;99(2):112-8. doi: 10.1007/s10266-011-0013-6. Epub 2011 May 7.
The response of bone cells to mechanical loading is mediated by the cytoskeleton. Since the bone anabolic agent fluoride disrupts the cytoskeleton, we investigated whether fluoride affects the response of bone cells to mechanical loading, and whether this is cytoskeleton mediated. The mechano-response of osteoblasts was assessed in vitro by measuring pulsating fluid flow-induced nitric oxide (NO) production. Osteocyte shape was determined in hamster mandibles in vivo as parameter of osteocyte mechanosensitivity. Pulsating fluid flow (0.7 ± 0.3 Pa, 5 Hz) stimulated NO production by 8-fold within 5 min. NaF (10-50 μM) inhibited pulsating fluid flow-stimulated NO production after 10 min, and decreased F-actin content by ~3-fold. Fluid flow-induced NO response was also inhibited after F-actin disruption by cytochalasin B. NaF treatment resulted in more elongated, smaller osteocytes in interdental bone in vivo. Our results suggest that fluoride inhibits the mechano-response of bone cells, which might occur via cytoskeletal changes. Since decreased mechanosensitivity reduces bone mass, the reported anabolic effect of fluoride on bone mass in vivo is likely mediated by other factors than changed bone cell mechanosensitivity.
细胞骨架介导了骨细胞对机械加载的反应。由于骨合成代谢药物氟化物会破坏细胞骨架，我们研究了氟化物是否会影响骨细胞对机械加载的反应，以及这种影响是否与细胞骨架有关。通过测量脉动液流诱导的一氧化氮（NO）产生，在体外评估成骨细胞的力学反应。体内通过检测仓鼠下颌骨中的骨细胞形状作为骨细胞机械敏感性的参数。脉动液流（0.7±0.3Pa，5Hz）在 5 分钟内刺激 NO 产生增加 8 倍。10 分钟后，NaF（10-50μM）抑制了脉动液流刺激的 NO 产生，并使 F-肌动蛋白含量减少约 3 倍。细胞松弛素 B 破坏 F-肌动蛋白后，也抑制了液流诱导的 NO 反应。NaF 处理导致体内牙间骨中骨细胞更细长、更小。我们的结果表明，氟化物抑制了骨细胞的力学反应，这可能是通过细胞骨架的变化发生的。由于机械敏感性降低会减少骨量，因此氟化物在体内对骨量的报道的合成代谢作用可能是通过改变骨细胞的机械敏感性以外的其他因素介导的。
