Parathyroid hormone signaling in mature osteoblasts/osteocytes protects mice from age-related bone loss.
Parathyroid hormone signaling in mature osteoblasts/osteocytes protects mice from age-related bone loss.
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DOI：
10.18632/aging.203808
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发表时间：
2021-12-30
期刊：
影响因子：
--
通讯作者：
Pajevic PD
中科院分区：
文献类型：
--
作者：
Uda Y;Saini V;Petty CA;Alshehri M;Shi C;Spatz JM;Santos R;Newell CM;Huang TY;Kochen A;Kim JW;Constantinou CK;Saito H;Held KD;Hesse E;Pajevic PD
衰老伴随着骨质减少，其特征在于骨形成减少和骨吸收增加。骨细胞是终末分化的成骨细胞，是骨稳态的调节者，并且成熟成骨细胞/骨细胞中的甲状旁腺激素（PTH）受体（PPR）信号传导对于PTH驱动的合成代谢和分解代谢骨骼反应是必需的。然而，PPR信号在这些细胞中的作用在衰老过程中尚未研究。本研究的目的是分析PTH信号在成熟成骨细胞/骨细胞衰老过程中的作用。骨细胞中缺乏PPR的小鼠（Dmp 1-PPRKO）表现出年龄依赖性骨质减少，其特征在于成骨细胞活性显著降低，破骨细胞数量和活性增加。在分子水平上，成熟成骨细胞/骨细胞中PPR信号传导的缺乏与血清硬化素的增加和表达氧化应激标志物4-羟基-2-壬烯醛的骨细胞的显著增加相关。在Dmp 1-PPRKO小鼠中，p16 Ink 4a/Cdkn 2a表达呈年龄依赖性增加，而在对照组中无变化。体外研究表明，PTH保护骨细胞免受氧化应激诱导的细胞死亡。总之，我们报道了骨细胞中的PPR信号通过抑制破骨细胞的活性和保护骨细胞免受氧化应激而对于保护骨骼免受年龄诱导的骨丢失是重要的。
Aging is accompanied by osteopenia, characterized by reduced bone formation and increased bone resorption. Osteocytes, the terminally differentiated osteoblasts, are regulators of bone homeostasis, and parathyroid hormone (PTH) receptor (PPR) signaling in mature osteoblasts/osteocytes is essential for PTH-driven anabolic and catabolic skeletal responses. However, the role of PPR signaling in those cells during aging has not been investigated. The aim of this study was to analyze the role of PTH signaling in mature osteoblasts/osteocytes during aging. Mice lacking PPR in osteocyte (Dmp1-PPRKO) display an age-dependent osteopenia characterized by a significant decrease in osteoblast activity and increase in osteoclast number and activity. At the molecular level, the absence of PPR signaling in mature osteoblasts/osteocytes is associated with an increase in serum sclerostin and a significant increase in osteocytes expressing 4-hydroxy-2-nonenals, a marker of oxidative stress. In Dmp1-PPRKO mice there was an age-dependent increase in p16Ink4a/Cdkn2a expression, whereas it was unchanged in controls. In vitro studies demonstrated that PTH protects osteocytes from oxidative stress-induced cell death. In summary, we reported that PPR signaling in osteocytes is important for protecting the skeleton from age-induced bone loss by restraining osteoclast’s activity and protecting osteocytes from oxidative stresses.
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影响因子：
5.5
作者：
Morimoto, Daiki;Kuroda, Shoko;Tomita, Tetsuya
通讯作者：
Tomita, Tetsuya
影响因子：
14.8
作者：
Ran, F. Ann;Hsu, Patrick D.;Zhang, Feng
通讯作者：
Zhang, Feng
成骨细胞中 TGF-β2 表达增加会导致骨质疏松症样表型。
DOI：
10.1083/jcb.132.1.195
发表时间：
1996-01
期刊：
The Journal of cell biology
影响因子：
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作者：
Erlebacher A;Derynck R
通讯作者：
Derynck R
影响因子：
6.2
作者：
Sinha, Partha;Aarnisalo, Piia;Wu, Joy Y.
通讯作者：
Wu, Joy Y.
通过多个内部控制基因的几何平均，对实时定量RT-PCR数据的准确归一化。
影响因子：
12.3
作者：
通讯作者：
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