title: Aging affects response to cyclic tensile stretch: paradigm for intervertebral disc degeneration.
abstract: Much evidence supports a fundamental role for mechanical forces in modulating differentiation, homeostasis, and remodelling of musculoskeletal cells. Little is known, however, regarding mechanobiology and gene expression of intervertebral disc (IVD) cells from older individuals. To characterise the effect of mechanical stimulation on cells from older discs, an in vitro study of IVD cells harvested from different aged pigs was conducted to measure extracellular matrix (ECM) gene expression in response to cyclic tensile stress (CTS). Gene expression of annulus fibrosus (AF) cells from IVDs of mature and older pigs was quantified for the predominant ECM genes; type I collagen, type II collagen and aggrecan, and matrix metalloproteinase 1 (MMP-1), a collagenase that degrades fibrillar collagens. AF cells cultured on flexible-bottom plates were stretched 10 % at 0.5 Hz frequency. After 24 h, gene expression was assayed using reverse transcriptase polymerase chain reaction (RT-PCR). Basal mRNA levels without stretching for type II collagen and aggrecan were lower in older annular cells whereas MMP-1 levels were higher compared to mature cells. Following CTS, an adaptive response was elicited in annular cells from both age groups. ECM protein genes were upregulated, whereas MMP-1 was downregulated. The magnitude of response was significantly greater in older cells as compared to mature cells. These data suggest that the cells from the AF of older animals manifest lower basal levels of mRNA for type II collagen and aggrecan and higher levels of MMP-1 possibly due to decreased tensile stress experienced in vivo and is not the result of reduced capacity for response.
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Hongsik
authors.initials: H
authors.lastname: Cho
authors.forename: Aman
authors.initials: A
authors.lastname: Seth
authors.forename: Jenna
authors.initials: J
authors.lastname: Warmbold
authors.forename: James T
authors.initials: JT
authors.lastname: Robertson
authors.forename: Karen A
authors.initials: KA
authors.lastname: Hasty
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000375:Aging; D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000473:pathology* / Q000503:physiopathology*; D017116:Low Back Pain; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013314:Stress, Mechanical; D013312:Stress, Physiological; D013552:Swine
chemical_list: D053674:Aggrecans; D024042:Collagen Type I; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D020781:Matrix Metalloproteinase 1