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  • Review Article
  • Published:

Intervertebral disc degeneration and osteoarthritis: a common molecular disease spectrum

Nature Reviews Rheumatology volume 19, pages 136–152 (2023)Cite this article

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Abstract

Intervertebral disc degeneration (IDD) and osteoarthritis (OA) affecting the facet joint of the spine are biomechanically interdependent, typically occur in tandem, and have considerable epidemiological and pathophysiological overlap. Historically, the distinctions between these degenerative diseases have been emphasized. Therefore, research in the two fields often occurs independently without adequate consideration of the co-dependence of the two sites, which reside within the same functional spinal unit. Emerging evidence from animal models of spine degeneration highlight the interdependence of IDD and facet joint OA, warranting a review of the parallels between these two degenerative phenomena for the benefit of both clinicians and research scientists. This Review discusses the pathophysiological aspects of IDD and OA, with an emphasis on tissue, cellular and molecular pathways of degeneration. Although the intervertebral disc and synovial facet joint are biologically distinct structures that are amenable to reductive scientific consideration, substantial overlap exists between the molecular pathways and processes of degeneration (including cartilage destruction, extracellular matrix degeneration and osteophyte formation) that occur at these sites. Thus, researchers, clinicians, advocates and policy-makers should consider viewing the burden and management of spinal degeneration holistically as part of the OA disease continuum.

Key points

  • Each functional spinal unit is made up of two vertebrae, one fibrocartilaginous intervertebral disc (IVD) joint and two conventional synovial facet joints.

  • Phenomenological features of IVD degeneration and facet joint osteoarthritis have considerable overlap, including the destruction of cartilage and other joint tissues, subchondral bone changes, osteophyte formation and reduced joint space.

  • Important overlapping endogenous molecular processes of IVD degeneration and facet joint osteoarthritis include extracellular matrix degeneration, inflammation, oxidative stress, apoptosis, senescence and reduced autophagy.

  • An important objective for the field will be to determine whether unique clinically relevant overlapping endotypes are present, which might correspond to a specific molecular process or biomarker.

  • Further unified studies are required that directly compare the molecular signatures of matched tissue samples from the IVD and facet joint using clinical samples and/or mouse models of disease progression.

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Fig. 1: Comparison of normal and degenerated vertebral and knee joints.
Fig. 2: Computer tomography images of endstage intervertebral disc and facet joint degeneration.
Fig. 3: Regional impact of alignment.
Fig. 4: Processes that promote pathology in IVD and OA.

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Acknowledgements

The work of R.R. and N.F. is supported by a J. Bernard Gosevitz Chair. The work of M.K. is supported in part by a Tier 1 Canada Research Chair in the mechanisms of joint degeneration and a Tony and Shari Fell Platinum Chair in Arthritis Research. The work of A.V.P. is supported by an award from Arthritis Society Canada (STAR-20-0000000012).

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Authors and Affiliations

  1. Osteoarthritis Research Program, Division of Orthopaedics, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada

    Noah Fine, Starlee Lively, Anthony V. Perruccio, Mohit Kapoor & Raja Rampersaud

  2. Krembil Research Institute, University Health Network, Toronto, Ontario, Canada

    Noah Fine, Starlee Lively, Anthony V. Perruccio, Mohit Kapoor & Raja Rampersaud

  3. Department of Physiology & Pharmacology, Schulich School of Medicine & Dentistry, Bone and Joint Institute, University of Western Ontario London, London, Ontario, Canada

    Cheryle Ann Séguin

  4. Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

    Anthony V. Perruccio

  5. Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

    Anthony V. Perruccio, Mohit Kapoor & Raja Rampersaud

  6. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Mohit Kapoor

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The authors contributed equally to all aspects of the article.

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Correspondence to Raja Rampersaud.

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Competing interests

R.R. and M.K. declare a US patent No US10888577B2: PCT international patent WO2017143430A1, entitled “MiRNA biomarkers for cartilage degeneration”. M.K. declares that he filed a US Provisional Patent Application no. 63/033,463, entitled “Circulating MicroRNAs in Early Knee Osteoarthritis and Uses Thereof”. The other authors declare no competing interests.

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Glossary

Adipokines

A class of cytokines produced by the adipose tissue.

Apoptosis

Programmed death of a cell.

Autophagy

A process by which cells break down and recycle intracellular components.

Notochord

An embryonic rod-like structure that functions as a precursor to the spine.

Osteophytes

Bony projections resulting from increased bone remodelling activity.

Pelvic incidence

A fixed, innate angle between the sacrum and pelvis that typically dictates the sagittal curvature of the mobile spine.

Sclerotome

The embryonic tissue that gives rise to the skeleton.

Senescence

The loss of proliferative potential in a cell.

Syndetome

An embryonic compartment that serves as a precursor that gives rise to the axial tendons.

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Fine, N., Lively, S., Séguin, C.A. et al. Intervertebral disc degeneration and osteoarthritis: a common molecular disease spectrum. Nat Rev Rheumatol 19, 136–152 (2023). https://doi.org/10.1038/s41584-022-00888-z

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