Abstract: Objective To investigate the effect and potential regulatory mechanism of histoneacetyltransferase P300 on the degeneration of nucleus pulposus cells (NPCs) in the intervertebral discs in the rat scoliosis model. Methods NPCs were cultured and divided into 4 groups: the untreated control group, the interleukin-1β ( IL-1β) -induced degeneration group ( IL-1β group), the IL-1β combined with P300 treatment group (IL-1β + P300 group), and the P300 treatment alone group ( P300 group). Cell proliferation activity was detected using the Cell Counting Kit-8 (CCK-8) assay. The levels of TNF-α and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). Cell apoptosis was determined using flow cytometry. The expression levels of sex determining region Y-box 9 ( SOX9 )、 collagen type Ⅱ ( COL-Ⅱ ), matrix metalloproteinase-13 (MMP-13), A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), inhibitor of nuclear factor-kappa B-α ( IκBα), phosphorylated IκBα ( p-IκBα), phosphorylated NF-κB P65 (p-P65), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in the cells were analyzed using Western blotting. Additionally, 40 adult specific pathogen-free (SPF) female SD rats were divided into 4 groups: sham surgery group, scoliosis model group, scoliosis model + P300 group, and scoliosis model + P300 + Nrf2-IN-3 group. The scoliosis model was established by removing the upper limbs and tail of the rats through surgery. In the scoliosis model + P300 group, P300 was intravenously injected [15 mg / (kg· d), 30 d] after modeling. In the scoliosis model + P300 + Nrf2-IN-3 group, P300 [15 mg / ( kg· d), 30 d] and the Nrf2 inhibitor Nrf2-IN-3 [23. 5 mg / ( kg · d), 30 d] were intravenously injected after modeling. After 30 days, the nucleus pulposus tissues from the T12-L1 intervertebral discs were collected, and the expression levels of SOX9, COL-Ⅱ , MMP-13, and ADAMTS-5 were determined usingWestern blotting. Results Compared with the control group, the IL-1β group showed decreasedcell viability, increased cell apoptosis, upregulated expression levels of TNF-α, IL-6, MMP-13, ADAMTS-5, p-P65, and p-IκBα, and downregulated expression levels of SOX9, COL-Ⅱ ,IκBα, Nrf2, and HO-1 (all P< 0. 05). Compared with the IL-1β group, the IL-1β + P300 groupshowed increased cell viability, decreased cell apoptosis, decreased expression levels of TNF-α, IL-6, MMP-13, ADAMTS-5, p-P65, and p-IκBα, and increased expression levels of SOX9,COL-Ⅱ , IκBα, Nrf2, and HO-1 ( all P < 0. 05). Compared with the sham surgery group, thescoliosis model group showed decreased expression levels of SOX9 and COL-Ⅱ , and increased expression levels of MMP-13 and ADAMTS-5 ( all P < 0. 05 ). Compared with the scoliosis modelgroup, the scoliosis model + P300 group showed increased expression levels of SOX9 and COL-Ⅱ ,and decreased expression levels of MMP-13 and ADAMTS-5 ( all P < 0. 05). Compared with thescoliosis model + P300 group, the scoliosis model + P300 + Nrf2-IN-3 group showed decreased expression levels of SOX9 and COL-Ⅱ , and increased expression levels of MMP-13 and ADAMTS-5(all P< 0. 05). Conclusion P300 inhibits intervertebral disc degeneration by regulating the Nrf2 /HO-1 / NF-κB signaling pathway in the rat scoliosis model.

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