EFFECT OF PH ON BONE-RESORPTION BY RAT OSTEOCLASTS INVITRO
EFFECT OF PH ON BONE-RESORPTION BY RAT OSTEOCLASTS INVITRO
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DOI：
10.1210/endo-119-1-119
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发表时间：
1986-07-01
期刊：
影响因子：
4.8
通讯作者：
DEMPSTER, DW
中科院分区：
文献类型：
--
作者：
ARNETT, TR;DEMPSTER, DW
酸中毒与各种代谢性骨病的发病机制有关。已知实验性的酸摄入刺激人体骨矿物质的释放，并增加动物的骨吸收表面，但其机制仍不清楚。我们研究了介质pH值对骨吸收活性的影响，在体外使用一种新的方法，允许直接测量骨吸收。破骨细胞从新生大鼠长骨中分解，并使其沉降到牛皮质骨薄片上。在培养基199中孵育24小时后，调节至所需的pH值，固定骨切片，并测定每个切片的吸收坑的数量和表面积。将培养基pH从7.4降低至6.8导致每个骨切片的平均吸收面积增加14倍（P < 0.01）。在pH 7.2和7.0下分别观察到5倍和9倍增加。骨细胞与人PTH-（1-34）（100/ng/ml）的孵育在pH 7.4或6.4下均未显著增强再吸收，而人降钙素（50 pg/ml）产生几乎完全抑制。所有处理均未改变平均破骨细胞和单核细胞数量。这是第一次直接证明低pH刺激细胞介导的骨吸收，这一观察结果可能具有相当大的生理和病理生理意义。
Acidosis has been implicated in the pathogenesis of various metabolic bone diseases. Experimental acid ingestion is known to stimulate the release of bone mineral in humans and increase osteoclastic resorption surfaces in animals, but the mechanism has remained unclear. We have investigated the effect of medium pH on osteoclastic activity in vitro using a new method that allows direct measurement of bone resorption. Osteoclasts were disaggregated from neonatal rat long bones and allowed to settle onto thin slices of bovine cortical bone. After 24-h incubation in medium 199, adjusted to the required pH, bone slices were fixed, and the number and surface area of resorption pits per slice were determined. Reduction in medium pH from 7.4 to 6.8 resulted in a 14-fold increase in the mean area resorbed per bone slice (P < 0.01). Five- and 9-fold increases were seen at pH 7.2 and 7.0, respectively. Incubation of bone cells with human PTH-(1-34) (100/ng/ml) did not significantly enhance resorption at either pH 7.4 or 6.4, whereas human calcitonin (50 pg/ml) produced near-total inhibition. Mean osteoclast and mononuclear cell numbers were unaltered by all treatments. This is the first direct demonstration that low pH stimulates cell-mediated bone resorption, an observation that may have considerable physiological and pathophysiological significance.