The mechanism study of THBS3 in regulating cartilage vascularization/bone coupling via the TGF-β/Smad2/3 pathway in osteoarthritis

Author:

Yan Jingyao1,Zhao Yanping1,Zhu Xiaoying1,Lu Hanya1,Wang Yanli1,Wang Shuya1,Zhang Zhiyi1

Affiliation:

1. First Affiliated Hospital of Harbin Medical University

Abstract

Abstract

Objective Vascularization and osteogenesis coupling is observed in osteoarthritis (OA) cartilage. THBS-3 belongs to the extracellular matrix (ECM) proteins and is highly expressed in cartilage tissue. The effect of THBS-3 on OA is unclear. This study aims to explore the mechanistic role of THBS-3 in OA. Design: Expressions of THBS-3 was detected by Western blot (WB) and RT-qPCR. WB was employed to measure the expression levels of synthesis and degradation metabolism, as well as vascularization/ossification coupling. Migration and tube formation experiments were conducted to assess the migratory and tube-forming abilities of HUVECs influenced by THBS-3. Micro-CT was utilized for 3D imaging in mice. Immunohistochemistry was employed to detect the expression of synthesis, degradation metabolism, and vascularization/ossification coupling-related markers. Additionally, WB was utilized to assess the transforming growth factor-beta (TGF-β) signaling pathway. Results Proteinomics sequencing has revealed a higher expression level of THBS-3 in OA cartilage. Chondrocytes from OA joints exhibited significantly higher expression of THBS-3 relative to healthy individuals. In experiments conducted both in vivo and in vitro, THBS-3 exhibited a dual impact by enhancing catabolic metabolism, suppressing synthetic metabolism, and fostering the coupling of vascularization and osteogenesis within the cartilage. THBS-3 activated the TGF-β signaling pathway, and blockade of the TGF-β signaling pathway resulted in increased p-Smad2/3 expression in OA cartilage cells and decreased expression of vascularization /ossification coupling. Conclusion THBS-3 can promote the vascularization/ossification coupling of cartilage cells by activating the TGF-β/Smad2/3 signaling pathway, providing new insights and targets for the treatment of OA.

Publisher

Research Square Platform LLC

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3