Mechanical Stress Induces Sodium Entry and Osmoprotective Responses in Murine Synovial Fibroblasts

兰克尔 细胞外 内分泌学 化学 骨保护素 内科学 骨重建 激活剂(遗传学) 前列腺素E2 细胞生物学 受体 生物 医学 生物化学
作者
Annemarie Proff,Ute Nazet,Agnes Schröder,Jonathan Jantsch
出处
期刊:Cells [Multidisciplinary Digital Publishing Institute]
卷期号:13 (6): 496-496
标识
DOI:10.3390/cells13060496
摘要

Osteoarthritis (OA) is a multifactorial disease depending on molecular, genetic, and environmental factors like mechanical strain. Next to the cartilage and the subchondral bone, OA also affects the synovium, which is critically involved in the maintenance of joint homeostasis. As there is a correlation between the extracellular sodium content in the knee joint and OA, this study investigates the impact of sodium on OA-associated processes like inflammation and bone remodeling without and with mechanical loading in synovial fibroblasts. For that purpose, murine synovial fibroblasts from the knee joint were exposed to three different extracellular sodium chloride concentrations (−20 mM, ±0 mM and +50 mM NaCl) in the absence or presence of compressive or intermittent tensile strain. In addition to the intracellular Na+ content and gene expression of the osmoprotective transcription factor nuclear factor of activated T cells 5 (Nfat5), the gene and protein expression of inflammatory mediators (interleukin-6 (IL6), prostaglandin endoperoxide synthase-2 (Ptgs2)/prostaglandin E2 (PGE2)), and factors involved in bone metabolism (receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG)) were analyzed by qPCR and ELISA. Mechanical strain already increased intracellular Na+ and Nfat5 gene expression at standard salt conditions to levels obtained by exposure to increased extracellular Na+ content. Both high salt and compressive strain resulted in elevated IL6 and PGE2 release. Intermittent tensile strain did not increase Il6 mRNA expression or IL6 protein secretion but triggered Ptgs2 expression and PGE2 production. Increased extracellular Na+ levels and compressive strain increased RANKL expression. In contrast, intermittent tension suppressed RANKL expression without this response being subject to modification by extracellular sodium availability. OPG expression was only induced by compressive strain. Changes in extracellular Na+ levels modified the inflammatory response and altered the expression of mediators involved in bone metabolism in cells exposed to mechanical strain. These findings indicate that Na+ balance and Nfat5 are important players in synovial fibroblast responses to mechanical stress. The integration of Na+ and Na+-dependent signaling will help to improve the understanding of the pathogenesis of osteoarthritis and could lead to the establishment of new therapeutic targets.

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
jhcraul完成签到,获得积分10
刚刚
芹菜完成签到,获得积分10
刚刚
胡子完成签到,获得积分10
刚刚
Luna发布了新的文献求助10
刚刚
夏天有空调哦完成签到,获得积分10
1秒前
fossil完成签到,获得积分10
1秒前
Hangerli完成签到,获得积分10
2秒前
airyletter完成签到,获得积分10
2秒前
charmander完成签到,获得积分10
2秒前
Butterfly完成签到,获得积分10
2秒前
waiho完成签到,获得积分10
2秒前
咪咪完成签到,获得积分10
2秒前
2秒前
唠叨的觅海完成签到,获得积分10
2秒前
3秒前
cyz完成签到 ,获得积分10
3秒前
程破茧完成签到,获得积分0
3秒前
高高冷风完成签到,获得积分10
3秒前
冷静剑成完成签到,获得积分10
3秒前
勤奋的安梦完成签到,获得积分10
3秒前
aeolianbells完成签到 ,获得积分10
3秒前
源宝发布了新的文献求助30
4秒前
斑斓椰奶冻完成签到,获得积分10
4秒前
青春发布了新的文献求助10
5秒前
情怀应助清秀黎昕采纳,获得10
5秒前
sagitar应助lamer采纳,获得40
5秒前
左安完成签到,获得积分10
5秒前
geold完成签到,获得积分10
6秒前
kkhenry发布了新的文献求助10
6秒前
小L想睡觉完成签到,获得积分10
6秒前
江川户牛牛完成签到,获得积分10
6秒前
huhu完成签到,获得积分10
7秒前
香蕉觅云应助1111采纳,获得30
7秒前
aaggaga完成签到,获得积分10
7秒前
David完成签到,获得积分20
7秒前
jiang完成签到 ,获得积分10
7秒前
健忘的醉蝶完成签到,获得积分10
8秒前
林初一发布了新的文献求助10
8秒前
8秒前
8秒前
高分求助中
Principles of Economics, 11th Edition 10000
University Physics with Modern Physics, 16th edition 10000
(应助此贴封号)【重要!!请各用户(尤其是新用户)详细阅读】【科研通的精品贴汇总】 10000
Arthritis and Related Conditions, An Issue of Orthopedic Clinics 1000
Development of a Bridge Weigh-In-Motion System: A technology to convert the bridge response to the passage of traffic into data on vehicle configurations, speeds, times of travel and weights 1000
ズームレンズの光学設計に関する研究 800
Fundamentals of Pharmaceutical and Biologics Regulations: A Global Perspective, Second Edition 700
热门求助领域 (近24小时)
化学 材料科学 医学 生物 纳米技术 工程类 有机化学 化学工程 生物化学 计算机科学 内科学 物理 复合材料 催化作用 细胞生物学 无机化学 光电子学 物理化学 电极 基因
热门帖子
关注 科研通微信公众号,转发送积分 7291094
求助须知:如何正确求助?哪些是违规求助? 8910084
关于积分的说明 18859173
捐赠科研通 6958530
什么是DOI,文献DOI怎么找? 3209298
关于科研通互助平台的介绍 2378998
邀请新用户注册赠送积分活动 2185014