University of Oulu

Francisco, V., Pino, J., González-Gay, M.Á. et al. A new immunometabolic perspective of intervertebral disc degeneration. Nat Rev Rheumatol 18, 47–60 (2022).

A new immunometabolic perspective of intervertebral disc degeneration

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Author: Francisco, Vera1; Pino, Jesús1; Ángel González-Gay, Miguel2;
Organizations: 1The NEIRID group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), C027-Research Laboratory 9, Santiago University Clinical Hospital, Santiago de Compostela, Spain
2Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Universidad de Cantabria and IDIVAL, Hospital Universitario Marqués de Valdecilla, Santander, Spain
3Molecular and Cellular Cardiology Group, SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), Research Laboratory 7, Santiago University Clinical Hospital, Santiago de Compostela, Spain
4Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
5Research 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
7University Medical Center Utrecht, Departments of Orthopedics, Rheumatology and Clinical Immunology, Utrecht, The Netherlands
8World Health Organization Collaborating Center for Public Health Aspects of Musculoskeletal Health and Aging, Université de Liège, Liège, Belgium
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
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Language: English
Published: Springer Nature, 2022
Publish Date: 2023-10-11


Intervertebral disc (IVD) degeneration is a common finding on spine imaging that increases in prevalence with age. IVD degeneration is a frequent cause of low back pain, which is a leading cause of disability. The process of IVD degeneration consists of gradual structural change accompanied by severe alterations in metabolic homeostasis. IVD degeneration, like osteoarthritis, is a common comorbidity in patients with obesity and type 2 diabetes mellitus, two metabolic syndrome pathological conditions in which adipokines are important promoters of low-grade inflammation, extracellular matrix degradation and fibrosis. Impairment in white adipose tissue function, due to the abnormal fat accumulation in obesity, is characterized by increased production of specific pro-inflammatory proteins such as adipokines by white adipose tissue and of cytokines such as TNF by immune cells of the stromal compartment. Investigations into the immunometabolic alterations in obesity and type 2 diabetes mellitus and their interconnections with IVD degeneration provide insights into how adipokines might affect the pathogenesis of IVD degeneration and impair IVD function and repair. Toll-like receptor-mediated signalling has also been implicated as a promoter of the inflammatory response in the metabolic alterations associated with IVD and is thus thought to have a role in IVD degeneration. Pathological starvation, obesity and adipokine dysregulation can result in immunometabolic alterations, which could be targeted for the development of new therapeutics.

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Series: Nature reviews. Rheumatology
ISSN: 1759-4790
ISSN-E: 1759-4804
ISSN-L: 1759-4790
Volume: 18
Issue: 1
Pages: 47 - 60
DOI: 10.1038/s41584-021-00713-z
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
3126 Surgery, anesthesiology, intensive care, radiology
Copyright information: © Springer Nature Limited 2021. This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: