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甲状旁腺激素信号在成熟成骨细胞/骨细胞中保护小鼠免受与年龄相关的骨丢失。

Parathyroid hormone signaling in mature osteoblasts/osteocytes protects mice from age-related bone loss.

机构信息

Department of Translational Dental Medicine, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA.

Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

出版信息

Aging (Albany NY). 2021 Dec 30;13(24):25607-25642. doi: 10.18632/aging.203808.

DOI:10.18632/aging.203808
PMID:34968192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8751595/
Abstract

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-PPR) 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-PPR mice there was an age-dependent increase in p16/ expression, whereas it was unchanged in controls. 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.

摘要

衰老是伴随着骨质疏松症的，其特征是骨形成减少和骨吸收增加。成骨细胞是终末分化的成骨细胞，是骨稳态的调节者，成熟成骨细胞/成骨细胞中的甲状旁腺激素 (PTH) 受体 (PPR) 信号对于 PTH 驱动的合成代谢和分解代谢骨骼反应是必不可少的。然而，PPR 信号在衰老过程中成骨细胞中的作用尚未被研究。本研究旨在分析 PTH 信号在成熟成骨细胞/成骨细胞中的作用衰老。缺乏成骨细胞中 PPR 的小鼠（Dmp1-PPR）表现出与年龄相关的骨质疏松症，其特征是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/成骨细胞中 PPR 信号的缺失与血清骨硬化素的增加以及表达 4-羟基-2-壬烯醛的成骨细胞数量的显著增加有关，这是氧化应激的标志物。在 Dmp1-PPR 小鼠中，p16/的表达随年龄增长而增加，而在对照组中则保持不变。研究表明，PTH 可保护成骨细胞免受氧化应激诱导的细胞死亡。总之，我们报告称，成骨细胞中的 PPR 信号对于通过抑制破骨细胞的活性和保护成骨细胞免受氧化应激来保护骨骼免受年龄相关的骨质流失是重要的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/a588ae9c8088/aging-13-203808-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/df17ad06fefa/aging-13-203808-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/ab0f974f7aa4/aging-13-203808-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/8c94375620f3/aging-13-203808-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/f8b4bafcc671/aging-13-203808-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/44c55020eef3/aging-13-203808-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/a588ae9c8088/aging-13-203808-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/df17ad06fefa/aging-13-203808-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/f6787372f847/aging-13-203808-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/ab0f974f7aa4/aging-13-203808-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/8c94375620f3/aging-13-203808-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/f8b4bafcc671/aging-13-203808-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/44c55020eef3/aging-13-203808-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b58/8751595/a588ae9c8088/aging-13-203808-g007.jpg

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