Anabolic actions of parathyroid hormone during bone growth are dependent on c-fos
Anabolic actions of parathyroid hormone during bone growth are dependent on c-fos
复制标题
DOI：
10.1210/en.2002-220221
复制
发表时间：
2002-10-01
期刊：
影响因子：
4.8
通讯作者：
McCauley, LK
中科院分区：
文献类型：
--
作者：
Demiralp, B;Chen, HL;McCauley, LK
PTH在骨中具有尚不清楚的合成代谢和分解代谢作用。原癌基因c-fos和其他活化蛋白1家族成员是骨中关键的转录介质，并且c-fos被PTH上调。本研究的目的是研究PTH的机制和c-fos在PTH介导的骨合成代谢中的作用。对c-fos（-/-）缺失的小鼠及其野生型（+/+）和杂合型（+/-）同窝小鼠给予PTH 17 d。PTH治疗后，+/+小鼠股骨骨矿物质密度（BMD）增加，而-/-小鼠BMD降低。PTH可增加+/+和-/-股骨的灰分重量，降低+/+或+/-股骨的钙含量，但不影响-/-股骨。组织形态学分析显示，甲状旁腺激素增加了c-fos +/+、+/-椎骨中的骨小梁体积，但相比之下，减少了-/-椎骨中的骨小梁体积。+/+小鼠的血清钙水平高于-/-小鼠，PTH增加-/-小鼠的钙。在组织学上，PTH导致-/-小鼠中已经加宽的生长板和肥大软骨细胞区的恶化，但不是增殖区。PTH还增加+/+小鼠的颅骨厚度，但不增加-/-小鼠的颅骨厚度。c-fos -/-小鼠有较低的骨唾液蛋白和骨钙素（OCN），但不变的PTH-1受体mRNA的表达在颅盖骨，表明细胞外基质的改变。急性甲状旁腺激素注射（8小时）导致骨钙素mRNA表达的野生型，但不变的表达-/-，颅盖骨。这些数据表明，c-fos在软骨内骨生长过程中PTH的合成代谢作用中起着关键作用。
PTH has anabolic and catabolic actions in bone that are not clearly understood. The protooncogene c-fos and other activating protein 1 family members are critical transcriptional mediators in bone, and c-fos is up-regulated by PTH. The purpose of this study was to examine the mechanisms of PTH and the role of c-fos in PTH-mediated anabolic actions in bone. Mice with ablation of c-fos (-/-) and their wild-type (+/+) and heterozygous (+/-) littermates were administered PTH for 17 d. The +/+ mice had increased femoral bone mineral density (BMD), whereas -/- mice had reduced BMD after PTH treatment. PTH increased the ash weight of +/+ and but not -/-, femurs and decreased the calcium content of but not +/+ or +/-, femurs. Histomorphometric analysis showed that PTH increased trabecular bone volume in c-fos +/+, +/- vertebrae, but, in contrast, decreased trabecular bone in -/- vertebrae. Serum calcium levels in +/+ mice were greater than those in -/- mice, and PTH increased calcium in -/- mice. Histologically, PTH resulted in an exacerbation of the already widened growth plate and zone of hypertrophic chondrocytes but not the proliferating zone in -/- mice. PTH also increased calvarial thickness in +/+ mice, but not -/- mice. The c-fos -/- mice had lower bone sialoprotein and osteocalcin (OCN), but unaltered PTH-1 receptor mRNA expression in calvaria, suggesting an alteration in extracellular matrix. Acute PTH injection (8 h) resulted in a decrease in osteocalcin mRNA expression in wild-type, but unaltered expression in -/-, calvaria. These data indicate that c-fos plays a critical role in the anabolic actions of PTH during endochondral bone growth.