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The response of nucleus pulposus cell senescence to static and dynamic compressions in a disc organ culture.

ABSTRACT: Mechanical stimuli obviously affect disc nucleus pulposus (NP) biology. Previous studies have indicated that static compression exhibits detrimental effects on disc biology compared with dynamic compression. To study disc NP cell senescence under static compression and dynamic compression in a disc organ culture, porcine discs were cultured and subjected to compression (static compression: 0.4 MPa for 4 h once per day; dynamic compression: 0.4 MPa at a frequency of 1.0 Hz for 4 h once per day) for 7 days using a self-developed mechanically active bioreactor. The non-compressed discs were used as controls. Compared with the dynamic compression, static compression significantly promoted disc NP cell senescence, reflected by the increased senescence-associated ?-galactosidase (SA-?-Gal) activity, senescence-associated heterochromatic foci (SAHF) formation and senescence markers expression, and the decreased telomerase (TE) activity and NP matrix biosynthesis. Static compression accelerates disc NP cell senescence compared with the dynamic compression in a disc organ culture. The present study provides that acceleration of NP cell senescence may be involved in previously reported static compression-mediated disc NP degenerative changes.

SUBMITTER: Shi J

PROVIDER: S-EPMC5843747 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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The response of nucleus pulposus cell senescence to static and dynamic compressions in a disc organ culture.

Shi Jianmin J Pang Lianglong L Jiao Shouguo S

Bioscience reports 20180309 2

Mechanical stimuli obviously affect disc nucleus pulposus (NP) biology. Previous studies have indicated that static compression exhibits detrimental effects on disc biology compared with dynamic compression. To study disc NP cell senescence under static compression and dynamic compression in a disc organ culture, porcine discs were cultured and subjected to compression (static compression: 0.4 MPa for 4 h once per day; dynamic compression: 0.4 MPa at a frequency of 1.0 Hz for 4 h once per day) f ...[more]

PMID: 29437905

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Project description:BackgroundThe development of mechanically active culture systems helps increase the understanding of the role of mechanical stress in intervertebral disc (IVD) degeneration. Motion segment cultures allow for preservation of the native IVD structure, and adjacent vertebral bodies facilitate the application and control of mechanical loads. The purpose of this study was to establish loading and organ culture methods for rabbit IVD motion segments to study the effect of static load on the whole disc organ.MethodsIVD motion segments were harvested from rabbit lumbar spines and cultured in no-loading 6-well plates (control conditions) or custom-made apparatuses under a constant, compressive load (3 kg, 0.5 MPa) for up to 14 days. Tissue integrity, matrix synthesis, and the matrix gene expression profile were assessed after 3, 7, and 14 days of culturing and compared with those of fresh tissues.ResultsThe results showed that ex vivo culturing of motion segments preserved tissue integrity under no-loading conditions for 14 days whereas the static load gradually destroyed the morphology after 3 days. Proteoglycan contents were decreased under both conditions, with a more obvious decrease under static load, and proteoglycan gene expression was also downregulated. However, under static load, immunohistochemical staining intensity and collagen Type II alpha 1 (COL2A1) gene expression were significantly enhanced (61.54 ± 5.91, P = 0.035) and upregulated (1.195 ± 0.040, P = 0.000), respectively, compared with those in the controls (P < 0.05). In contrast, under constant compression, these trends were reversed. Our initial results indicated that short-term static load stimulated the synthesis of collagen Type II alpha 1; however, sustained constant compression led to progressive degeneration and specifically to a decreased proteoglycan content.ConclusionsA loading and organ culture system for ex vivo rabbit IVD motion segments was developed. Using this system, we were able to study the effects of mechanical stimulation on the biology of IVDs, as well as the pathomechanics of IVD degeneration.

Project description:Intervertebral disc (IVD) degeneration is a complicated physiological change involving cellular senescence, inflammation and the degradation of the extracellular matrix. Long non?coding RNAs (lncRNAs) have been identified as new players in IVD degeneration. The present study aimed to identify lncRNAs implicated in IVD degeneration via the regulation of cellular senescence. In the present study, nucleus pulposus (NP) cells isolated from moderately degenerated IVD tissues exhibited a senescent phenotype with increased senescence rates, detected by senescence?associated ??galactosidase (SA???gal) staining, and reduced growth and migratory abilities. Microarray and target prediction analyses identified 353 differentially expressed lncRNAs, and 251 cis? and 2,170 trans?acting targets in degenerated NP cells. Bioinformatic analyses revealed that these predicted targets were enriched in the regulation of response to DNA damage stimulus, positive regulation of cell cycle processes and interferon?? production. In addition, a network of the top 10 upregulated and top 10 downregulated lncRNA targets was constructed, and two trans?acting targets, C?C motif chemokine ligand 5 (CCL5) and polyribonucleotide nucleotidyltransferase 1 (PNPT1) involved in aging or senescence, and their corresponding lncRNAs, lnc?ST8SIA5?1:2 and lnc?HRK?2:1, were identified. Reverse transcription?quantitative PCR validation demonstrated that the two targets and two candidate lncRNAs were significantly upregulated in degenerated NP cells. Overexpression of lnc?HRK?2:1, with validated higher expression levels, in normal NP cells induced a senescent phenotype, with enhanced rates of senescence detected by SA???gal staining in cells, decreased growth and migratory abilities and improved expression levels of CCL5 and PNPT1. Collectively, these results suggested that upregulation of lnc?HRK?2:1 prompted NP cell senescence in IVD degeneration, which may be associated with increased expression levels of CCL5 and PNPT1.

Dataset Information

The response of nucleus pulposus cell senescence to static and dynamic compressions in a disc organ culture.

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The response of nucleus pulposus cell senescence to static and dynamic compressions in a disc organ culture.

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