Mice lacking substance P have normal bone modeling but diminished bone formation, increased resorption, and accelerated osteopenia with aging.
Mice lacking substance P have normal bone modeling but diminished bone formation, increased resorption, and accelerated osteopenia with aging.
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缺乏物质P的小鼠具有正常的骨建模，但骨形成减少，吸收增加并随着衰老而加速骨质减少。
DOI：
10.1016/j.bone.2020.115806
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发表时间：
2021-03
期刊：
影响因子：
4.1
通讯作者：
Kingery WS
中科院分区：
文献类型：
--
作者：
Wang L;Hou S;Sabsovich I;Guo TZ;Wei T;Kingery WS
P 物质 (SP) 是一种感觉神经肽，由支配骨骼的神经元表达。有大量证据表明 SP 可以在体外调节骨细胞功能，但尚不清楚 SP 是否在体内调节骨建模或重塑。为了回答这个问题，我们对表达 SP 的 Tac1 基因缺失的小鼠的骨表型进行了表征。通过使用 μCT 成像、静态和动态骨组织形态计量学以及尿脱氧吡啶啉交联 (DPD) 测量来表征 2 个月大和 5 个月大 SP 缺陷小鼠及其野生型对照的表型。 2 个月龄时，没有观察到 2 个品系的骨表型存在差异。 5个月时，野生型和SP缺陷型小鼠都出现了松质性骨质减少，但相对于野生型小鼠，SP缺陷型小鼠的松质骨损失明显更大。 SP缺陷小鼠还表现出骨形成减少、破骨细胞数量增加和尿DPD水平增加。缺乏 SP 的 5 个月大小鼠的皮质缺损早期修复被延迟。总的来说，这些发现表明 SP 信号传导不是骨建模所必需的，但 SP 信号传导可减少与年龄相关的骨质减少并加速皮质缺损修复，数据支持 SP 是骨代谢的合成代谢生理调节剂的假设。
Substance P (SP) is a sensory neuropeptide that is expressed by the neurons innervating bone. There is considerable evidence that SP can regulate bone cell function in vitro, but it is unclear whether SP modulates bone modeling or remodeling in vivo. To answer this question we characterized the bone phenotype of mice with deletion of the Tac1 gene expressing SP. The phenotypes of 2-month-old and 5-month-old SP deficient mice and their wildtype controls were characterized by using μCT imaging, static and dynamic bone histomorphometry, and urinary deoxypyridinoline cross-links (DPD) measurement. No differences in bone phenotypes were observed between the 2 strains at 2 months of age. By 5 months both the wildtype and SP deficient mice had developed cancellous osteopenia, but relative to the wild-type mice the SP deficient mice had significantly greater cancellous bone loss. The SP deficient mice also exhibited decreased bone formation, increased osteoclast number, and increased urinary DPD levels. Cortical defect early repair was delayed in 5-month-old mice lacking SP. Collectively, these findings indicate that SP signaling is not required for bone modeling, but SP signaling reduces age-related osteopenia and accelerates cortical defect reparation, data supporting the hypothesis that SP is an anabolic physiologic regulator of bone metabolism.
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影响因子：
3
作者：
Akopian, A;Demulder, A;Bergmann, P
通讯作者：
Bergmann, P
影响因子：
3.6
作者：
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2.5
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作者：
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影响因子：
4.1
作者：
Kingery, WS;Offley, SC;Jacobs, CR
通讯作者：
Jacobs, CR