Chronic metabolic acidosis alters osteoblast differentiation from human mesenchymal stem cells
Chronic metabolic acidosis alters osteoblast differentiation from human mesenchymal stem cells
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DOI：
10.1038/sj.ki.5002035
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发表时间：
2007-02-01
影响因子：
19.6
通讯作者：
Rajatanavin, R.
中科院分区：
文献类型：
--
作者：
Disthabanchong, S.;Radinahamed, P.;Rajatanavin, R.
远端肾小管酸中毒患者的骨组织学显示骨形成减少，骨基质矿化受损，这不能完全用矿物质平衡的改变来解释。体外研究的数据表明代谢性酸中毒对成骨细胞功能有直接抑制作用。我们研究了慢性代谢性酸中毒对间充质干细胞（MSC）分化为成骨细胞的影响。人类间充质干细胞在培养物中分化为成骨细胞。将浓盐酸添加到培养基中以降低碳酸氢盐浓度和pH。检查了各种成骨细胞基因和蛋白质的表达以及骨基质矿化。慢性代谢性酸中毒会增强早期成骨细胞转录因子runx-2的信使RNA（mRNA）和蛋白质表达，而抑制osterix并对ATF-4没有影响。 I 型胶原蛋白（最丰富的骨基质蛋白）的表达按照与 runx-2 相同的模式增加。同样，代谢性酸中毒略微增强了成熟成骨细胞基因骨钙素的表达。矿化研究表明碱性磷酸酶 mRNA 和酶活性受到抑制。尽管酸性培养物中胶原蛋白沉积增加，但骨基质矿化受到损害。总之，慢性代谢性酸中毒通过对成骨细胞基因和蛋白质的不同影响，改变成骨细胞与间充质干细胞的分化，从而导致骨形成受损。
Bone histology of distal renal tubular acidosis patients showed decreased bone formation with impaired bone matrix mineralization that is not entirely explained by an alteration in the mineral balance. Data from in vitro studies suggests a direct inhibitory effect of metabolic acidosis on osteoblast function. We investigated the effects of chronic metabolic acidosis on osteoblast differentiation from mesenchymal stem cells ( MSCs). Human MSCs were allowed to differentiate into osteoblasts in culture. Concentrated hydrochloric acid was added to the medium to lower the bicarbonate concentration and pH. The expression of various osteoblastic genes and proteins and bone matrix mineralization were examined. Chronic metabolic acidosis enhanced the messenger RNA ( mRNA) and protein expression of early osteoblast transcription factor, runx-2, whereas inhibiting osterix and having no effect on ATF-4. The expression of type I collagen, the most abundant bone matrix protein, was increased following the same pattern of runx-2. Likewise, metabolic acidosis slightly enhanced the expression of mature osteoblastic gene, osteocalcin. Study on mineralization revealed suppressed alkaline phosphatase mRNA and enzyme activity. Despite the augmented collagen deposit in acidic culture, bone matrix mineralization was impaired. In conclusion, chronic metabolic acidosis alters osteoblast differentiation from MSCs through its diverse effect on osteoblastic genes and proteins resulting in an impairment of bone formation.