Amphiregulin lacks an essential role for the bone anabolic action of parathyroid hormone
Amphiregulin lacks an essential role for the bone anabolic action of parathyroid hormone
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DOI：
10.1016/j.mce.2015.09.031
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发表时间：
2015-12-05
影响因子：
4.1
通讯作者：
Erben, Reinhold G.
中科院分区：
文献类型：
--
作者：
Jay, Freya F.;Vaidya, Mithila;Erben, Reinhold G.
虽然甲状旁腺激素(PTH)在间歇给药时一直被认为是一种骨合成代谢剂，但其确切的潜在机制在很大程度上仍不清楚。两亲性调节蛋白(AREG)是表皮生长因子受体的配体，在体内外已被证实是甲状旁腺激素的靶基因。在这里，我们使用雌性全局AREG基因敲除(AREG-KO)小鼠来探讨AREG在甲状旁腺素的骨合成代谢效应中的作用。与野生型对照组相比，AREG-KO小鼠在3个月和8个月龄时股骨远端松质骨量没有变化，而股骨中段的骨密度(BMD)和皮质厚度仅轻微下降。AREG缺乏与3周龄小鼠股骨松质骨成骨细胞中其他EGFR配体基因表达的复杂变化有关。为了研究在没有和存在AREG的情况下PTH对骨骼合成代谢的影响，我们在4周内每周给3月龄AREG-KO雌性和野生型对照仔鼠注射80µg/kg PTH或赋形剂5次。间歇性PTH治疗AREG-KO小鼠导致股骨小梁和皮质骨密度、皮质厚度、皮质内和骨膜骨形成、松质骨形成率和血清骨钙素增加，与野生型对照小鼠观察到的结果相当。总之，我们的数据表明甲状旁腺素的骨合成作用不需要AREG，至少在3个月大的雌性小鼠中是这样。(C)2015年提交人。由爱思唯尔爱尔兰有限公司出版。这是CC BY-NC-ND许可证(http://creativecommons.org/licenses/by-nc-nd/4.0/).下的一篇开放获取文章
Although parathyroid hormone (PTH) has long been known to act as a bone anabolic agent when administered intermittently, the exact underlying mechanisms remain largely unknown. Amphiregulin (AREG), a ligand of the epidermal growth factor receptor, has been identified to be a PTH target gene in vitro and in vivo. Here, we used female global AREG knockout (AREG-KO) mice to explore the role of AREG in mediating the bone anabolic effects of PTH. AREG-KO mice were characterized by unchanged distal femoral cancellous bone mass and only subtle decreases in bone mineral density (BMD) and cortical thickness at the femoral midshaft at 3 and 8 months of age, relative to wildtype controls. AREG deficiency was associated with complex changes in the mRNA expression of other EGFR ligands in femoral cancellous bone osteoblasts in situ in 3-week-old mice. To examine the bone anabolic effects of PTH in the absence and presence of AREG, we injected 3-month-old AREG-KO females and wildtype control littermates with 80 mu g/kg PTH or vehicle 5 times per week over 4 weeks. Intermittent PTH treatment of AREG-KO mice led to increases in femoral trabecular and cortical BMD, cortical thickness, endocortical and periosteal bone formation, cancellous bone formation rate, and serum osteocalcin, comparable to those observed in wildtype control mice. In conclusion, our data indicate that the bone anabolic effects of PTH do not require AREG, at least in 3-month-old female mice. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).