NiHHTP Attenuates Intervertebral Disc Degeneration via Necroptosis Inhibition: Mechanistic Insights from Integrated In Vitro and In Vivo Models

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Abstract

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain, with necroptosis playing a pivotal role in its pathogenesis. This study investigates the potential of Material NIHHTP in mitigating IVDD by inhibiting necroptosis. Nucleus pulposus (NP) cell cultures and a lumbar puncture-induced IVDD mouse model were employed to assess the effects of NIHHTP. Western blot (WB) analysis was conducted to evaluate necroptosis markers, including receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), mixed lineage kinase domain-like protein (MLKL), and their phosphorylated forms. Additionally, histological analyses, including hematoxylin-eosin (HE) staining, safranin O-fast green staining, and immunofluorescence, were performed to assess tissue integrity and protein expression. Our results demonstrate that NIHHTP confers protection against intervertebral disc degeneration by targeting and inhibiting necroptotic signaling pathways, underscoring its promise as a potential therapeutic approach for treating disc degeneration.

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