Mechanical vibration inhibits osteoclast formation by reducing DC-STAMP receptor expression in osteoclast precursor cells.
Mechanical vibration inhibits osteoclast formation by reducing DC-STAMP receptor expression in osteoclast precursor cells.
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DOI：
10.1016/j.bone.2013.08.020
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发表时间：
2013-12
期刊：
影响因子：
4.1
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Kulkarni RN;Voglewede PA;Liu D
众所周知，缺乏身体活动会导致肌肉质量损失，但也会导致骨质流失。从机制上讲，破骨细胞生成和骨吸收最近已被证明受振动调节。然而，抑制破骨细胞形成的潜在机制尚不清楚。因此，我们研究了破骨细胞前体细胞的机械振动是否通过融合相关分子（例如树突状细胞特异性跨膜蛋白（DC-STAMP）和P2X7受体（P2X7R）的参与）影响破骨细胞的形成。用 20 ng/ml NF-κB 配体受体激活剂 (RANKL) 处理 RAW264.7（鼠破骨细胞样细胞系）细胞。连续 3 天，将细胞以 4 Hz 的频率进行 1 小时、位移 20 µm 的机械振动，并与在相同条件下处理但没有振动的对照细胞进行比较。培养5天后，测定破骨细胞的形成。机械振动1小时后测定RAW264.7细胞的DC-STAMP和P2X7R的基因表达，而振动后孵育6小时后测定DC-STAMP的蛋白质产量。结果，RAW264.7细胞的机械振动抑制了破骨细胞的形成。 RANKL 存在时振动将 DC-STAMP 基因表达下调 1.6 倍，RANKL 不存在时振动下调 1.4 倍。此外，在 RAW264.7 细胞中，响应机械振动，在 RANKL 存在的情况下 DC-STAMP 蛋白的产生也下调了 1.4 倍，在 RANKL 不存在的情况下下调了 1.2 倍。然而，振动并不影响P2X7R基因的表达。小鼠抗 DC-STAMP 抗体在没有振动的情况下抑制破骨细胞形成。我们的结果表明，破骨细胞前体细胞的机械振动会降低破骨细胞前体细胞中 DC-STAMP 的表达，从而抑制破骨细胞的形成。
It is well known that physical inactivity leads to loss of muscle mass, but it also causes bone loss. Mechanistically, osteoclastogenesis and bone resorption have recently been shown to be regulated by vibration. However, the underlying mechanism behind the inhibition of osteoclast formation is yet unknown. Therefore, we investigated whether mechanical vibration of osteoclast precursor cells affects osteoclast formation by the involvement of fusion-related molecules such as dendritic cell-specific transmembrane protein (DC-STAMP), and P2X7 receptor (P2X7R). RAW264.7 (a murine osteoclastic-like cell line) cells were treated with 20 ng/ml receptor activator of NF-κB ligand (RANKL). For 3 consecutive days, the cells were subjected to 1 hour of mechanical vibration with 20 µm displacement at a frequency of 4 Hz and compared to the control cells that were treated under the same condition but without the vibration. After 5 days of culture, osteoclast formation was determined. Gene expression of DC-STAMP and P2X7R by RAW264.7 cells were determined after 1 hour mechanical vibration, while protein production of the DC-STAMP was determined after 6 hours of post incubation after vibration. As a result, mechanical vibration of RAW264.7 cells inhibited the formation of osteoclasts. Vibration down-regulated DC-STAMP gene expression by 1.6-fold in the presence of RANKL and by 1.4-fold in the absence of RANKL. Additionally, DC-STAMP protein production was also down-regulated by 1.4-fold in the presence of RANKL and by 1.2-fold in the absence of RANKL in RAW264.7 cells in response to mechanical vibration. However, vibration did not affect P2X7R gene expression. Mouse anti-DC-STAMP antibody inhibited osteoclast formation in the absence of vibration. Our results suggest that mechanical vibration of osteoclast precursor cells reduce DC-STAMP expression in osteoclast precursor cells leading to the inhibition of osteoclast formation.