Monomeric CRP regulates inflammatory responses in human intervertebral disc cells

Bone & Joint Research

article

Clara Ruiz-Fernández¹  Djedjiga Ait Eldjoudi¹  Maria González-Rodríguez¹  Alfonso Cordero Barreal¹  Yousof Farrag¹  Lucia García-Caballero²  Francisca Lago³  Ali Mobasheri⁴  Daisuke Sakai⁵  Jesús Pino¹  Oreste Gualillo¹ 

[1] SERGAS ,(Galician Healthcare Service) and NEIRID Lab ,(Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, IDIS ,(Health Research Institute of Santiago de Compostela), University Clinical Hospital of Santiago de Compostela;Department of Morphological Sciences, University of Santiago de Compostela;Molecular and Cellular Cardiology Group, SERGAS ,(Galician Healthcare Service) and IDIS ,(Health Research Institute of Santiago de Compostela), Research Laboratory 7, University Clinical Hospital of Santiago de Compostela;Research Unit of Medical Imaging, Physics, and Technology, Faculty of Medicine, University of Oulu;Department of Orthopedic Surgery, Surgical Science, School of Medicine, Tokai University

关键词: Monomeric CRP;    Inflammation;    Intervertebral disc;    Annulus fibrosus;    Nucleus pulposus;    Low back pain;    CRP;    intervertebral disc (IVD);    matrix metalloproteinase 13;    interleukin;    quantitative real-time polymerase chain reaction;    mRNA;    western blot;    annulus fibrosus (AF) tissue;    IL-8;    RNA;   

DOI  :  10.1302/2046-3758.123.BJR-2022-0223.R1

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsCRP 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.MethodsWe 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.ResultsWe 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.ConclusionOur 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.

【 授权许可】

CC BY-NC