Loss of signal transducer and activator of transcription 3 in osteoblasts impaired the bone healing in inflammatory microenvironment.

IF 2.8 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Molecular Oral Microbiology Pub Date : 2024-06-01 Epub Date: 2023-06-22 DOI:10.1111/omi.12425

Jingyi Feng, Zijing Huang, Jiarui Lu, Laiting Chan, Xin Feng, Lizhen Lei, Zhuwei Huang, Lichieh Lin, Yichen Yao, Xiaolei Zhang

{"title":"Loss of signal transducer and activator of transcription 3 in osteoblasts impaired the bone healing in inflammatory microenvironment.","authors":"Jingyi Feng, Zijing Huang, Jiarui Lu, Laiting Chan, Xin Feng, Lizhen Lei, Zhuwei Huang, Lichieh Lin, Yichen Yao, Xiaolei Zhang","doi":"10.1111/omi.12425","DOIUrl":null,"url":null,"abstract":"Introduction: This study aimed to investigate the effect of Stat3 on the osteoblast-mediated bone healing in the inflammatory lesion.Methods: The conditional knockout of Stat3 in osteoblasts (Stat3 CKO) was generated via the Cre-loxP recombination system using Osterix-Cre transgenic mice. The calvarial bone inflammatory lesions were established on both Stat3 CKO and wild-type mice, then harvested to assess the bone healing. In response to lipopolysaccharide (LPS) stimulation, osteoblasts from Stat3 CKO and wild-type mice were subjected to examine the formation of calcium deposits, the expression of osteogenic markers (i.e., Runx2, OPN, COL1A1), and osteoclast-related markers (i.e., RANKL, OPG). The EdU and transwell assays were performed to assess the proliferation and migration of the cells.Results: A decrease in bone mass and an increase in osteolysis were found in the inflammatory lesions on Stat3 CKO mice when compared with the control. More osteoclastic-like cells and an increased expression of RANKL were observed in Stat3 CKO mice. Both mRNA and protein expressions of Stat3 and osteogenic markers in the lesions were significantly decreased in Stat3 CKO mice. After co-cultured with osteogenic medium, the Stat3-deficient osteoblasts were found with a significant decrease in calcium deposits and the expression of osteogenic markers, and with a significant increased expression of RANKL. The impaired ossification of Stat3-deficient osteoblasts was even more pronounced with the presence of lipopolysaccharides in vitro. The most decrease in cell proliferation and migration was found in Stat3-deficient osteoblasts in response to LPS.Conclusions: Loss of Stat3 in osteoblasts impaired bone healing in an inflammatory microenvironment.","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Oral Microbiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/omi.12425","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: This study aimed to investigate the effect of Stat3 on the osteoblast-mediated bone healing in the inflammatory lesion.

Methods: The conditional knockout of Stat3 in osteoblasts (Stat3 CKO) was generated via the Cre-loxP recombination system using Osterix-Cre transgenic mice. The calvarial bone inflammatory lesions were established on both Stat3 CKO and wild-type mice, then harvested to assess the bone healing. In response to lipopolysaccharide (LPS) stimulation, osteoblasts from Stat3 CKO and wild-type mice were subjected to examine the formation of calcium deposits, the expression of osteogenic markers (i.e., Runx2, OPN, COL1A1), and osteoclast-related markers (i.e., RANKL, OPG). The EdU and transwell assays were performed to assess the proliferation and migration of the cells.

Results: A decrease in bone mass and an increase in osteolysis were found in the inflammatory lesions on Stat3 CKO mice when compared with the control. More osteoclastic-like cells and an increased expression of RANKL were observed in Stat3 CKO mice. Both mRNA and protein expressions of Stat3 and osteogenic markers in the lesions were significantly decreased in Stat3 CKO mice. After co-cultured with osteogenic medium, the Stat3-deficient osteoblasts were found with a significant decrease in calcium deposits and the expression of osteogenic markers, and with a significant increased expression of RANKL. The impaired ossification of Stat3-deficient osteoblasts was even more pronounced with the presence of lipopolysaccharides in vitro. The most decrease in cell proliferation and migration was found in Stat3-deficient osteoblasts in response to LPS.

Conclusions: Loss of Stat3 in osteoblasts impaired bone healing in an inflammatory microenvironment.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

成骨细胞中信号转导和转录激活因子 3 的缺失会损害炎症微环境中的骨愈合。

引言本研究旨在探讨 Stat3 对炎性病变中成骨细胞介导的骨愈合的影响：方法：利用 Osterix-Cre 转基因小鼠，通过 Cre-loxP 重组系统，在成骨细胞中条件性敲除 Stat3（Stat3 CKO）。在 Stat3 CKO 小鼠和野生型小鼠的腓骨上建立骨炎性病变，然后采集病变组织以评估骨愈合情况。在脂多糖（LPS）刺激下，Stat3 CKO小鼠和野生型小鼠的成骨细胞被检测钙沉积的形成、成骨标志物（如Runx2、OPN、COL1A1）和破骨细胞相关标志物（如RANKL、OPG）的表达。EdU和Transwell试验用于评估细胞的增殖和迁移：结果：与对照组相比，Stat3 CKO 小鼠炎症病变部位的骨量减少，骨溶解增加。在 Stat3 CKO 小鼠中观察到了更多的破骨细胞和更高的 RANKL 表达。Stat3 CKO 小鼠病灶中 Stat3 和成骨标志物的 mRNA 和蛋白表达量均显著下降。在与成骨培养基共同培养后，发现 Stat3 缺失的成骨细胞的钙沉积和成骨标志物的表达明显减少，而 RANKL 的表达明显增加。在体外存在脂多糖的情况下，Stat3缺陷成骨细胞的骨化障碍更为明显。Stat3缺陷的成骨细胞对LPS的反应中，细胞增殖和迁移的下降幅度最大：结论：成骨细胞中 Stat3 的缺失会损害炎症微环境中的骨愈合。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Molecular Oral Microbiology DENTISTRY, ORAL SURGERY & MEDICINE-MICROBIOLOGY

CiteScore

6.50

自引率

5.40%

发文量

审稿时长

>12 weeks

期刊介绍： Molecular Oral Microbiology publishes high quality research papers and reviews on fundamental or applied molecular studies of microorganisms of the oral cavity and respiratory tract, host-microbe interactions, cellular microbiology, molecular ecology, and immunological studies of oral and respiratory tract infections. Papers describing work in virology, or in immunology unrelated to microbial colonization or infection, will not be acceptable. Studies of the prevalence of organisms or of antimicrobials agents also are not within the scope of the journal. The journal does not publish Short Communications or Letters to the Editor. Molecular Oral Microbiology is published bimonthly.