1. Bradykinin protects nucleus pulposus cells from tert-butyl hydroperoxide-induced damage and delays intervertebral disc degeneration.
- Author
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Qiu X, Ma C, Luo Z, Zhang Y, Kang J, Zhu D, Wang Z, Li L, Wei Z, Wang Z, and Kang X
- Subjects
- Animals, Female, Humans, Male, Rats, Cells, Cultured, Disease Models, Animal, Microspheres, Phosphatidylinositol 3-Kinases metabolism, Polylactic Acid-Polyglycolic Acid Copolymer chemistry, Proto-Oncogene Proteins c-akt metabolism, Rats, Sprague-Dawley, Receptor, Bradykinin B2 metabolism, Signal Transduction drug effects, Apoptosis drug effects, Bradykinin pharmacology, Intervertebral Disc Degeneration drug therapy, Intervertebral Disc Degeneration pathology, Nucleus Pulposus drug effects, Nucleus Pulposus pathology, Nucleus Pulposus metabolism, Oxidative Stress drug effects, tert-Butylhydroperoxide toxicity
- Abstract
Intervertebral disc degeneration (IVDD) is a leading cause of degenerative spinal disorders, involving complex biological processes. This study investigates the role of the kallikrein-kinin system (KKS) in IVDD, focusing on the protective effects of bradykinin (BK) on nucleus pulposus cells (NPCs) under oxidative stress. Clinical specimens were collected, and experiments were conducted using human and rat primary NPCs to elucidate BK's impact on tert-butyl hydroperoxide (TBHP)-induced oxidative stress and damage. The results demonstrate that BK significantly inhibits TBHP-induced NPC apoptosis and restores mitochondrial function. Further analysis reveals that this protective effect is mediated through the BK receptor 2 (B2R) and its downstream PI3K/AKT pathway. Additionally, BK/PLGA sustained-release microspheres were developed and validated in a rat model, highlighting their potential therapeutic efficacy for IVDD. Overall, this study sheds light on the crucial role of the KKS in IVDD pathogenesis and suggests targeting the B2R as a promising therapeutic strategy to delay IVDD progression and promote disc regeneration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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