Inhibition of PHOSPHO1 activity results in impaired skeletal mineralization during limb development of the chick
Inhibition of PHOSPHO1 activity results in impaired skeletal mineralization during limb development of the chick
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DOI：
10.1016/j.bone.2009.12.018
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发表时间：
2010-04-01
期刊：
影响因子：
4.1
通讯作者：
Farquharson, Colin
中科院分区：
文献类型：
--
作者：
MacRae, Vicky E.;Davey, Megan G.;Farquharson, Colin
PHOSPHO 1是一种骨特异性磷酸酶，参与启动基质矿化的无机磷酸盐生成。矿化的控制归因于组织非特异性碱性磷酸酶（TNAP）的作用。然而，含有磷灰石晶体的基质囊泡（MV）存在于低磷酸盐血症患者以及TNAP null（Akp 2（-/-））小鼠中。尽管PHOSPHO 1和TNAP的表达与MV有关，但在肢体发育的早期阶段PHOSPHO 1和TNAP是否共同表达尚不清楚。此外，PHOSPHO 1在基质矿化中的功能性体内作用尚未确定。在此，我们研究了PHOSPHO 1在鸡肢芽间充质微团培养物中以及在野生型和talpid突变体中的时间表达和功能作用。这些突变体的特点是有缺陷的刺猬信号和endochondrium mineralization.The能力的体外微团培养分化和矿化其基质的表达增加的PHOSPHO 1和TNAP的时间相关。在发育中的胚胎腿（发育阶段23- 36 HH）中观察到表达的可比变化。用兰索拉唑（一种磷酸化酶1活性的小分子抑制剂）或FGF 2（一种软骨细胞分化的抑制剂）处理的微团培养物导致茜素红染色减少（P
PHOSPHO1 is a bone-specific phosphatase implicated in the initiation of inorganic phosphate generation for matrix mineralization. The control of mineralization is attributed to the actions of tissue-nonspecific alkaline phosphatase (TNAP). However, matrix vesicles (MVs) containing apatite crystals are present in patients with hypophosphatasia as well as TNAP null (Akp2(-/-)) mice. It is therefore likely that other phosphatases work with TNAP to regulate matrix mineralization.Although PHOSPHO1 and TNAP expression is associated with MVs, it is not known if PHOSPHO1 and TNAP are coexpressed during the early stages of limb development. Furthermore, the functional in vivo role of PHOSPHO1 in matrix mineralization has yet to be established. Here, we studied the temporal expression and functional role of PHOSPHO1 within chick limb bud mesenchymal micromass cultures and also in wild-type and talpid(3) chick mutants. These mutants are characterized by defective hedgehog signalling and the absence of endochondral mineralization.The ability of in vitro micromass cultures to differentiate and mineralize their matrix was temporally associated with increased expression of PHOSPHO1 and TNAP. Comparable changes in expression were noted in developing embryonic legs (developmental stages 23-36HH). Micromass cultures treated with lansoprazole, a small-molecule inhibitor of PHOSPHO1 activity, or FGF2, an inhibitor of chondrocyte differentiation, resulted in reduced alizarin red staining (P