Antithetic effects of ryanodine and ruthenium red on osteoclast-mediated bone resorption and intracellular calcium concentrations.
Antithetic effects of ryanodine and ruthenium red on osteoclast-mediated bone resorption and intracellular calcium concentrations.
复制标题
兰尼定和钌红对破骨细胞介导的骨吸收和细胞内钙浓度的对抗作用。
DOI：
10.1002/jcb.240590216
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Fitzpatrick,LA
中科院分区：
文献类型：
--
作者：
Ritchie,CK;Strei,TA;Maercklein,PB;Fitzpatrick,LA
在骨重建过程中，破骨细胞负责骨吸收。高水平的细胞内钙降低破骨细胞的骨吸收活性，并增加破骨细胞从骨表面的脱离。细胞内钙离子在骨吸收中的调节作用尚不清楚。为了理解这一现象，我们研究了细胞内钙调节剂兰尼定和钌红对骨吸收的影响，使用分解破骨细胞坑分析。用荧光探针fura 2检测用这些化合物处理后细胞内钙浓度的变化。使用ryanodine时，检测到骨吸收显著、剂量依赖性降低。这种对骨吸收的抑制作用在去除ryanodine后是可逆的。Ryanodine增加细胞内钙浓度，表明Ryanodine的抑制机制是通过改变细胞内钙的储存。钌红处理后，破骨细胞吸收的骨显著多于溶剂处理的细胞。这种骨吸收的增加与细胞内钙浓度的降低相关。在含有兰尼定的破骨细胞培养物中加入甲状旁腺激素或钌红并不能减弱兰尼定引起的骨吸收减少，这表明兰尼定抑制骨吸收的机制可能涉及钙通道在开放位置的“锁定”。© 1995 Wiley利斯公司
In the process of bone remodeling, osteoclasts are responsible for resorption of bone. High levels of intracellular calcium decrease the bone resorbing activity of osteoclasts and increase detachment of osteoclasts from the bone surface. The regulatory role of intracellular calcium in bone resorption is not clearly understood. To understand this phenomenon, we studied the effects of the intracellular calcium modulators ryanodine and ruthenium red on bone resorption using the disaggregated osteoclast pit assay. Changes in intracellular calcium concentrations after treatment with these compounds were detected with the fluoroprobe fura2. With ryanodine, a significant, dose‐dependent decrease in bone resorption was detected. This inhibition of bone resorption was reversible upon the removal of ryanodine. Ryanodine increased intracellular calcium concentrations, suggesting that the mechanism of inhibition by ryanodine was via alterations in intracellular stores of calcium. After treatment with ruthenium red, osteoclasts resorbed significantly more bone compared to vehicle‐treated cells. This increase in bone resorption correlated with a decrease in intracellular calcium concentrations. The addition of parathyroid hormone or ruthenium red to osteoclast cultures containing ryanodine did not attenuate the decrease in bone resorption caused by ryanodine, suggesting that the mechanism of ryanodine inhibition of bone resorption may involve the “locking” of a calcium channel in an open position. © 1995 Wiley‐Liss, Inc.