免疫印迹
促炎细胞因子
分子生物学
椎间盘
PI3K/AKT/mTOR通路
炎症
基质金属蛋白酶
激酶
信号转导
细胞生物学
化学
生物
免疫学
生物化学
解剖
基因
作者
Clara Ruiz-Fernández,Djedjiga Ait Eldjoudi,María González-Rodriguez,Alfonso Cordero-Barreal,Yousof Farrag,Lucía García‐Caballero,Francisca Lago,Ali Mobasheri,Daisuke Sakai,Jesús Pino,Oreste Gualillo
出处
期刊:Bone and Joint Research
[British Editorial Society of Bone and Joint Surgery]
日期:2023-03-08
卷期号:12 (3): 189-198
被引量:2
标识
DOI:10.1302/2046-3758.123.bjr-2022-0223.r1
摘要
CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration. We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry. We demonstrated that mCRP increases nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX2), matrix metalloproteinase 13 (MMP13), vascular cell adhesion molecule 1 (VCAM1), interleukin (IL)-6, IL-8, and Lipocalin 2 (LCN2) expression in human AF and NP cells. We also showed that nuclear factor-κβ (NF-κβ), extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphoinositide 3-kinase (PI3K) are at play in the intracellular signalling of mCRP. Finally, we demonstrated the presence of mCRP in human AF and NP tissues. Our results indicate, for the first time, that mCRP can be localized in IVD tissues, where it triggers a proinflammatory and catabolic state in degenerative and healthy IVD cells, and that NF-κβ signalling may be implicated in the mediation of this mCRP-induced state.
科研通智能强力驱动
Strongly Powered by AbleSci AI