title: Mitochondrial bioenergetics, mass, and morphology are altered in cells of the degenerating human annulus.
abstract: Back pain and intervertebral disc degeneration have a growing socioeconomic healthcare impact. Information on mitochondrial function in human intervertebral disc cells, however, is surprisingly sparse. We assessed mitochondrial bioenergetics, mass, and ultrastructure in annulus cells cultured from human discs of varying degenerative stages. Citrate synthase activity (reflecting mitochondrial mass) declined significantly with increasing Thompson grade (p < 0.0001). Both mitochondrial (p = 0.009) and non-mitochondrial (p = 0.0029) respiration showed significant changes with increasing stages of disc degeneration. No significant relationships were found for the association of respiration data with herniated or non-herniated status, or with subject age. Examination of mitochondrial ultrastructure in cultured annulus cells revealed unusual features which included mitochondrial inclusion bodies, poorly defined cristae and dark staining. Findings reported here are novel and document biochemical, metabolic, and morphologic abnormalities in mitochondria in cells from more degenerated annulus cells. Data suggest that the disc degenerative, not age, is a major factor associated with mitochondrial impairment, and also implicate oxidative stress, driven by mitochondrial dysfunction, as a major component within the degenerating disc. Findings have relevance to advancements in cell-based therapies to treat disc degeneration.
authors.affiliation: Department of Orthopaedic Surgery, Orthopaedic Research Biology, Cannon Research, Room 304, Carolinas Medical Center, P.O. Box 32861, Charlotte, North Carolina 28232, USA. helen.gruber@carolinashealthcare.org
authors.forename: Helen E
authors.initials: HE
authors.lastname: Gruber
authors.forename: John A
authors.initials: JA
authors.lastname: Watts
authors.forename: Frank E
authors.initials: FE
authors.lastname: Riley
authors.forename: Mary-Beth
authors.initials: MB
authors.lastname: Fulkerson
authors.forename: H James
authors.initials: HJ
authors.lastname: Norton
authors.forename: Edward N
authors.initials: EN
authors.lastname: Hanley
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D002950:Citrate (si)-Synthase / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D055959:Intervertebral Disc Degeneration / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology* / Q000473:pathology* / Q000648:ultrastructure; D053142:Mitochondrial Size; D018384:Oxidative Stress; D010101:Oxygen Consumption; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D002950:Citrate (si)-Synthase