Kariya Taro, Tanabe Natsuko, Shionome Chieko, Manaka Soichiro, Kawato Takayuki, Zhao Ning, Maeno Masao, Suzuki Naoto, Shimizu Noriyoshi
Nihon University Graduate School of Dentistry, Tokyo, Japan.
J Cell Biochem. 2015 Jan;116(1):12-21. doi: 10.1002/jcb.24863.
Orthodontic tooth movement induces alveolar bone resorption and formation by mechanical stimuli. Force exerted on the traction side promotes bone formation. Adenosine triphosphate (ATP) is one of the key mediators that respond to bone cells by mechanical stimuli. However, the effect of tension force (TF)-induced ATP on osteogenesis is inadequately understood. Accordingly, we investigated the effect of TF on ATP production and osteogenesis in MC3T3-E1 cells. Cells were incubated in the presence or absence of P2X7 receptor antagonist A438079, and then stimulated with or without cyclic TF (6% or 18%) for a maximum of 24 h using Flexercell Strain Unit 3000. TF significantly increased extracellular ATP release compared to control. Six percent TF had maximum effect on ATP release compared to 18% TF and control. Six percent TF induced the expression of Runx2 and Osterix. Six percent TF also increased the expression of extracellular matrix proteins (ECMPs), ALP activity, and the calcium content in ECM. A438079 blocked the stimulatory effect of 6% TF on the expression of Runx2, Osterix and ECMPs, ALP activity, and calcium content in ECM. This study indicated that TF-induced extracellular ATP is released in osteoblasts, suggesting that TF-induced ATP promotes osteogenesis by autocrine action through P2X7 receptor in osteoblasts.
正畸牙齿移动通过机械刺激诱导牙槽骨吸收和形成。施加在牵引侧的力促进骨形成。三磷酸腺苷（ATP）是通过机械刺激对骨细胞作出反应的关键介质之一。然而，张应力（TF）诱导的ATP对成骨作用的影响尚未得到充分了解。因此，我们研究了TF对MC3T3-E1细胞中ATP产生和成骨作用的影响。将细胞在存在或不存在P2X7受体拮抗剂A438079的情况下孵育，然后使用Flexercell Strain Unit 3000在有或没有循环TF（6%或18%）的情况下刺激长达24小时。与对照组相比，TF显著增加了细胞外ATP释放。与18%TF和对照组相比，6%TF对ATP释放的影响最大。6%TF诱导了Runx2和Osterix的表达。6%TF还增加了细胞外基质蛋白（ECMPs）的表达、碱性磷酸酶（ALP）活性以及细胞外基质中的钙含量。A438079阻断了6%TF对Runx2、Osterix和ECMPs表达、ALP活性以及细胞外基质中钙含量的刺激作用。本研究表明，TF诱导的细胞外ATP在成骨细胞中释放，提示TF诱导的ATP通过成骨细胞中P2X7受体的自分泌作用促进成骨。
