title: Molecular basis of intervertebral disc degeneration and herniations: what are the important translational questions?
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.
authors.affiliation: 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.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Kadow
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Sowa
authors.forename: Nam
authors.initials: N
authors.lastname: Vo
authors.forename: James D
authors.initials: JD
authors.lastname: Kang
mesh_terms: D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D055959:Intervertebral Disc Degeneration / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D007405:Intervertebral Disc Displacement / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D019637:Orthopedic Procedures; D010447:Peptide Hydrolases / Q000378:metabolism; D011237:Predictive Value of Tests; D012307:Risk Factors; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D016326:Extracellular Matrix Proteins; D018836:Inflammation Mediators; D010447:Peptide Hydrolases