Extracellular pH regulates bone cell function
Extracellular pH regulates bone cell function
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DOI：
10.1093/jn/138.2.415s
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发表时间：
2008-02-01
影响因子：
4.2
通讯作者：
Arnett, Timothy R.
中科院分区：
文献类型：
--
作者：
Arnett, Timothy R.
陆地脊椎动物的骨骼含有大量的碱性矿物(羟基磷灰石)，如果酸碱平衡不能保持在狭窄的范围内，这些矿物最终可用于缓冲代谢H(+)。酸中毒对骨骼的负面影响早已为人所知，但被认为是由于骨矿物质被动的物理化学溶解所致。这篇简短的、选择性的综述总结了目前已知的骨细胞对细胞外pH的直接功能反应。我们发现，酸直接刺激培养的破骨细胞发生骨吸收。当pH为7.0时，刺激作用接近最大，高于7.4时，吸收关闭。在骨器官培养中，H(+)刺激的骨矿物质释放几乎完全是由破骨细胞介导的，几乎没有物理化学成分。酸化是破骨细胞挖掘吸收陷窝的关键条件，因此细胞外H(+)可能被认为是长期寻找的破骨细胞激活因子。酸激活的破骨细胞可被甲状旁腺激素、1，25-二羟基胆钙素和核因子-kappaB受体激活剂等进一步刺激。破骨细胞可能通过H(+)敏感离子通道对pH变化作出反应，如瞬时受体电位香草素1，一种也可被辣椒素激活的伤害性感受器。酸中毒对培养的成骨细胞的骨基质矿化也有很强的相互抑制作用。这是由于低pH值下羟基磷灰石的溶解度增加，以及矿化所需的碱性磷酸酶受到选择性抑制所致。向碱性方向改变酸碱平衡的饮食或药物可能会为骨丢失疾病提供有用的治疗方法。
The skeletons of land vertebrates contain a massive reserve of alkaline mineral (hydroxyapatite), which is ultimately available to buffer metabolic H(+) if acid-base balance is not maintained within narrow limits. The negative impact of acidosis on the skeleton has long been known but was thought to result from passive, physicochemical dissolution of bone mineral. This brief, selective review summarizes what is now known of the direct functional responses of bone cells to extracellular pH. We discovered that bone resorption by cultured osteoclasts is stimulated directly by acid. The stimulatory effect is near-maximal at pH 7.0, whereas above pH 7.4, resorption is switched off. In bone organ cultures, H(+)-stimulated bone mineral release is almost entirely osteoclast-mediated, with a negligible physicochemical component. Acidification is the key requirement for osteoclasts to excavate resorption pits in all species studied to date, and extracellular H(+) may thus be regarded as the long-sought osteoclast activation factor. Acid-activated osteoclasts can be stimulated further by agents such as parathyroid hormone, 1,25-dihydroxycholecalciferol, and receptor activator of nuclear factor kappa B ligand. Osteoclasts may respond to pH changes via H(+)-sensing ion channels such as transient receptor potential vanilloid 1, a nociceptor that is also activated by capsaicin. Acidosis also exerts a powerful, reciprocal inhibitory effect on the mineralization of bone matrix by cultured osteoblasts. This is caused by increased hydroxyapatite solubility at low pH, together with selective inhibition of alkaline phosphatase, which is required for mineralization. Diets or drugs that shift acid-base balance in the alkaline direction may provide useful treatments for bone loss disorders.