title: Intervertebral disc cell response to dynamic compression is age and frequency dependent.
abstract: The maintenance of the intervertebral disc extracellular matrix is regulated by mechanical loading, nutrition, and the accumulation of matrix proteins and cytokines that are affected by both aging and degeneration. Evidence suggests that cellular aging may lead to alterations in the quantity and quality of extracellular matrix produced. The aims of this study were to examine the role of loading and maturation (a subset of aging), and the interaction between these two factors in intervertebral disc cell gene expression and biosynthesis in a controlled 3D culture environment. Cells were isolated from young (4-6 months) and mature (18-24 months) bovine caudal annulus fibrosus and nucleus pulposus tissue. Isolated cells were seeded into alginate and dynamically compressed for 7 days at either 0.1, 1, or 3 Hz or maintained as a free-swelling control. After 7 days, DNA and sulfated glycosaminoglycan contents were analyzed along with real time, quantitative reverse transcription-polymerase chain reaction analysis for collagen types I and II, aggrecan, and matrix metalloproteinase-3 gene expression. Results suggest that maturation plays an important role in intervertebral disc homeostasis and influences the cell response to mechanical loading. While isolated intervertebral disc cells responded to mechanical compression in 3D culture, the effect of loading frequency was minimal. Altered cellular phenotype and biosynthesis rates appear to be an attribute of the cell maturation process, potentially independent of changes in cellular microenvironment associated with lost nutrition and disc degeneration. Mature cells may have a decreased capacity to create or retain extracellular matrix components in response to mechanical loading compared to young cells.
authors.affiliation: Spine Bioengineering Lab, College of Engineering and Mathematical Sciences, University of Vermont, Burlington, Vermont 05405, USA.
authors.forename: Casey L
authors.initials: CL
authors.lastname: Korecki
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Kuo
authors.forename: Rocky S
authors.initials: RS
authors.lastname: Tuan
authors.forename: James C
authors.initials: JC
authors.lastname: Iatridis
mesh_terms: D000367:Age Factors; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000464:Alginates; D000818:Animals; D002417:Cattle; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D019245:Compressive Strength / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D020723:Glucuronic Acid; D006025:Glycosaminoglycans / Q000235:genetics / Q000378:metabolism; D006603:Hexuronic Acids; D007403:Intervertebral Disc / Q000166:cytology* / Q000502:physiology*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D053674:Aggrecans; D000464:Alginates; D024042:Collagen Type I; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D006603:Hexuronic Acids; C013786:A73025; D020723:Glucuronic Acid; D019278:Matrix Metalloproteinase 3