EXTRACELLULAR PROTONS ACIDIFY OSTEOCLASTS, REDUCE CYTOSOLIC CALCIUM, AND PROMOTE EXPRESSION OF CELL-MATRIX ATTACHMENT STRUCTURES
EXTRACELLULAR PROTONS ACIDIFY OSTEOCLASTS, REDUCE CYTOSOLIC CALCIUM, AND PROMOTE EXPRESSION OF CELL-MATRIX ATTACHMENT STRUCTURES
复制标题
DOI：
10.1172/jci114235
复制
发表时间：
1989-09-01
影响因子：
15.9
通讯作者：
HRUSKA, KA
中科院分区：
文献类型：
--
作者：
TETI, A;BLAIR, HC;HRUSKA, KA
由于代谢酸在体外和体内都能刺激骨吸收，所以我们重点关注酸中毒产生的细胞事件，这些事件可能与刺激骨重建有关。为此，我们将分离的鸡破骨细胞暴露在代谢性(丁酸)酸中，观察到细胞内pH和细胞内钙([Ca+]i)的下降。当通过HCO3负载碱化的骨吸收细胞被转移到无重碳酸盐的环境中时，这些现象被重述。酸诱导的破骨细胞[Ca~(2+)]i下降可被NaCN、NaCN或Na3VO4以非Na+依赖的方式阻断，尽管每种抑制剂都未能改变刺激的细胞内酸化。此外，K+诱导的膜去极化也降低了胞内钙离子，这种作用与质子的作用相辅相成。这些发现表明，附着在骨上的破骨细胞缺乏功能性的电压操纵性钙通道，它们通过驻留在膜上的Ca-ATPase来降低[Ca+]i对质子的反应。最重要的是，酸中毒促进了足小体的形成，足小体是破骨细胞透明区的接触区，表明与基质的粘附性增加，这是骨吸收的早期步骤。因此，破骨细胞的胞外酸化导致细胞内pH和钙的降低，并似乎促进了细胞-基质的附着。
Because metabolic acids stimulate bone resorption in vitro and in vivo, we focused on the cellular events produced by acidosis that might be associated with stimulation of bone remodeling. To this end, we exposed isolated chicken osteoclasts to a metabolic (butyric) acid and observed a fall in both intracellular pH and cytosolic calcium ([Ca2+]i). These phenomena were recapitulated when bone resorptive cells, alkalinized by HCO3- loading, were transferred to a bicarbonate-free environment. The acid-induced decline in osteoclast [Ca2+]i was blocked either NaCN or NaCN or NA3VO4, in a Na+-independent fashion, despite the failure of each inhibitor to alter stimulated intracellular acidification. Moreover, K+-induced membrane depolarization also reduced cytosolic calcium in a manner additive to the effect of protons. These findings suggest that osteoclasts adherent to bone lack functional voltage-operated Ca2+ channels, and they reduce [Ca2+]i in response to protons via a membrane residing Ca-ATPase. Most importantly, acidosis enhances formation of podosomes, the contact areas of the osteoclast clear zone, indicating increased adhesion to substrate, an early step in bone resorption. Thus, extracellular acidification of osteoclasts leads to decrements in intracellular pH and calcium, and appears to promote cell-matrix attachment.