Phosphate regulates embryonic endochondral bone development.
Phosphate regulates embryonic endochondral bone development.
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DOI：
10.1002/jcb.22302
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发表时间：
2009-10-15
影响因子：
4
通讯作者：
Demay, Marie B.
中科院分区：
文献类型：
--
作者：
Zalutskaya, Alena A.;Cox, Megan K.;Demay, Marie B.
生长板成熟过程中肥大软骨细胞终末分化需要磷酸盐。软骨细胞分化的体外模型表明，7 mM磷酸盐，浓度类似于妊娠晚期胎儿，激活肥大软骨细胞中的线粒体凋亡途径。这就提出了一个问题，即细胞外磷酸盐是否调节胚胎软骨内骨形成过程中软骨细胞的分化和凋亡。为了解决这个问题，我们在小鼠跖骨培养模型中进行了研究，该模型重现了体内骨发育。跖骨用1.25 mM和7 mM磷酸盐培养4、8和12天。与在1.25 mM磷酸盐中培养的跖骨相比，用7 mM磷酸盐培养的跖骨显示增殖减少。这种增殖的减少伴随着肥大软骨细胞分化的早期增强，与FGF 18表达的增加相关。通过培养8天，在7 mM磷酸盐中培养的跖骨中观察到肥大软骨细胞的caspase-9活化和凋亡增加。胚胎骨的免疫组织化学分析表明，在肥大软骨细胞中，caspase-9的活化与血管浸润有关。因此，这些研究表明，磷酸盐促进软骨细胞分化在胚胎发育过程中，并暗示磷酸盐激活的线粒体凋亡途径在胚胎软骨内骨形成的生理作用。
Phosphate is required for terminal differentiation of hypertrophic chondrocytes during postnatal growth plate maturation. In vitro models of chondrocyte differentiation demonstrate that 7mM phosphate, a concentration analogous to that of the late gestational fetus, activates the mitochondrial apoptotic pathway in hypertrophic chondrocytes. This raises the question as to whether extracellular phosphate modulates chondrocyte differentiation and apoptosis during embryonic endochondral bone formation. To address this question, we performed investigations in the mouse metatarsal culture model that recapitulates in vivo bone development. Metatarsals were cultured for 4, 8 and 12 days with 1.25 mM and 7 mM phosphate. Metatarsals cultured with 7 mM phosphate showed a decrease in proliferation compared to those cultured in 1.25 mM phosphate. This decrease in proliferation was accompanied by an early enhancement in hypertrophic chondrocyte differentiation, associated with an increase in FGF18 expression. By 8 days in culture, an increase caspase-9 activation and apoptosis of hypertrophic chondrocytes was observed in the metatarsals cultured in 7 mM phosphate. Immunohistochemical analyses of embryonic bones demonstrated activation of caspase-9 in hypertrophic chondrocytes, associated with vascular invasion. Thus, these investigations demonstrate that phosphate promotes chondrocyte differentiation during embryonic development and implicate a physiological role for phosphate activation of the mitochondrial apoptotic pathway during embryonic endochondral bone formation.
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影响因子：
--
作者：
KLEMENT, BJ;SPOONER, BS
通讯作者：
SPOONER, BS
DOI：
10.1016/0169-6009(91)90028-x
发表时间：
1991-03-01
期刊：
BONE AND MINERAL
影响因子：
--
作者：
MINKIN, C;STJAMES, S;MARKS, SC
通讯作者：
MARKS, SC
影响因子：
4.1
作者：
Legeai-Mallet, L;Benoist-Lasselin, C;Bonaventure, J
通讯作者：
Bonaventure, J
影响因子：
10.5
作者：
Sahni, M;Ambrosetti, DC;Basilico, C
通讯作者：
Basilico, C
DOI：
10.1073/pnas.0502249102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Sabbagh, Y;Carpenter, TO;Demay, MB
通讯作者：
Demay, MB