University of Oulu

Bone Joint Res 2023;12(3):189–198,

Monomeric CRP regulates inflammatory responses in human intervertebral disc cells

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Author: Ruiz-Fernández, C.1,2; Eldjoudi, D. Ait1; González-Rodríguez, M.1;
Organizations: 1SERGAS (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, Santiago de Compostela, Spain
2Doctoral Programme in Medicine Clinical Research, International PhD School of the University of Santiago de Compostela (EDIUS), Santiago de Compostela, Spain
3Department of Morphological Sciences, University of Santiago de Compostela, Santiago de Compostela, Spain
4Molecular 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, Santiago de Compostela, Spain
5Recearch Unit of Medical Imaging, Physics, and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
6Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
7Departments of Orthopedic, Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
8World Health Organization Collaborating Center for Public Health Aspects of Musculoskeletal Health and Aging, University of Liège, Liège, Belgium
9Department of Orthopedic Surgery, Surgical Science, School of Medicine, Tokai University, Isehara, Japan
10Traumatology and Orthopedics Area, Department of Surgery and Medical- Surgical Specialties, University of Santiago de Compostela, Santiago de Compostela, Spain
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.4 MB)
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Language: English
Published: British Editorial Society of Bone and Joint Surgery, 2023
Publish Date: 2023-08-18


Aims: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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Series: Bone & joint Research
ISSN: 2046-3758
ISSN-E: 2046-3758
ISSN-L: 2046-3758
Volume: 12
Issue: 3
Pages: 189 - 198
DOI: 10.1302/2046-3758.123.BJR-2022-0223.R1
Type of Publication: A1 Journal article – refereed
Field of Science: 3126 Surgery, anesthesiology, intensive care, radiology
Funding: The authors disclose receipt of the following financial or material support for the research, authorship, and/or publication of this article: funding from the ISCIII (Instituto de Salud Carlos III) and The European Regional Development Fund (ERDF-FEDER) (grant PI20/00902). The authors report that they received open access funding for their manuscript by grant PI20/00902 funded by ISCIII (Instituto de Salud Carlos III) and The European Regional Development Fund (ERDF-FEDER).
Copyright information: © 2023 Author(s) et al. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credited. See