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Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions?

  • Symposium: Current Approaches to the Management of Lumbar Disc Herniation
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Intervertebral disc degeneration is a common condition with few inexpensive and effective modes of treatment, but current investigations seek to clarify the underlying process and offer new treatment options. It will be important for physicians to understand the molecular basis for the pathology and how it translates to developing clinical treatments for disc degeneration. In this review, we sought to summarize for clinicians what is known about the molecular processes that causes disc degeneration.

Results

A healthy disc requires maintenance of a homeostatic environment, and when disrupted, a catabolic cascade of events occurs on a molecular level resulting in upregulation of proinflammatory cytokines, increased degradative enzymes, and a loss of matrix proteins. This promotes degenerative changes and occasional neurovascular ingrowth potentially contributing to the development of pain. Research demonstrates the molecular changes underlying the harmful effects of aging, smoking, and obesity seen clinically while demonstrating the variable influence of exercise. Finally, oral medications, supplements, biologic treatments, gene therapy, and stem cells hold great promise but require cautious application until their safety profiles are better outlined.

Conclusions

Intervertebral disc degeneration occurs where there is a loss of homeostatic balance with a predominantly catabolic metabolic profile. A basic understanding of the molecular changes occurring in the degenerating disc is important for practicing clinicians because it may help them to inform patients to alter lifestyle choices, identify beneficial or harmful supplements, or offer new biologic, genetic, or stem cell therapies.

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Acknowledgments

We thank the staff of Ferguson Laboratory for Orthopaedic and Spine Research for their support and guidance in selecting topics for discussion in this manuscript.

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Authors and Affiliations

  1. Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, University of Pittsburgh, E1641 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA, 15261, USA

    Tiffany Kadow MD, Nam Vo PhD & James D. Kang MD

  2. Ferguson Laboratory for Orthopaedic and Spine Research, Department of Physical Medicine and Rehabilitation, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA

    Gwendolyn Sowa MD, PhD

Authors
  1. Tiffany Kadow MD
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  2. Gwendolyn Sowa MD, PhD
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  3. Nam Vo PhD
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  4. James D. Kang MD
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Corresponding author

Correspondence to James D. Kang MD.

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Kadow, T., Sowa, G., Vo, N. et al. Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions?. Clin Orthop Relat Res 473, 1903–1912 (2015). https://doi.org/10.1007/s11999-014-3774-8

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