HBP1 deficiency protects against stress-induced premature senescence of nucleus pulposus

W. Liu, W.-C. Li, X.-F. Pan, H. Sha, W.-Q. Gong, M. Yan

Department of Spine Surgery, The First Hospital of Jilin University, Changchun, China. 5296827@qq.com

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• Orthopedics

OBJECTIVE: Senescence of nucleus pulposus (NP) cells is involved in the pathological process of intervertebral disc degeneration (IVDD). HMG-box transcription factor 1 (HBP1) is a transcriptional inhibitor that prevents proliferation and regulates premature senescence of cells. The aim of this study was to confirm whether HBP1 deficiency could protect stress-induced NP cells premature senescence.

PATIENTS AND METHODS: Firstly, HBP1 protein level in human degenerated intervertebral disc tissues was detected. Then, NP cells were isolated from disc samples and transfected with plasmid to upregulate HBP1expression. H2O2 and interleukin-1b (IL-1b) were used to induce NP cells premature senescence in a different manner. Thereafter, cell viability, proliferation, and apoptosis were measured, and the protein expressions of collagen II, HBP1, and p16, were determined by Western blot or immunofluorescence. Finally, the mRNA levels of aggrecan, collagen I, IL-6, Transforming Growth Factor-α (TNF-α), and matrix metalloproteinase-3 (MMP-3) were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR).

RESULTS: The data indicated that HBP1 was upregulated in degenerated NP tissues. HBP1 gene overexpression increased p16 expression, affected NP cell proliferation, and caused cell apoptosis. In addition, HBP1 also decreased the collagen II and aggrecan expressions but increased collagen I, IL-6, TNF-α, and MMP-3 levels. Moreover, the silencing of HBP1 markedly reversed the H2O2 and IL-1b induced NP cell senescence by reducing p16 expression, apoptotic cell population, and inflammatory response and by promoting cell proliferation.

CONCLUSIONS: In summary, HBP1 accumulation contributes to the senescence of NP cells, and HBP1 deficiency protects stress-induced NP cells premature senescence.

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