Bradykinin protects nucleus pulposus cells from tert-butyl hydroperoxide-induced damage and delays intervertebral disc degeneration

Xiaoming Qiu; Chongwen Ma; Zhangbin Luo; Yibao Zhang; Jihe Kang; Daxue Zhu; Zhaoheng Wang; Lei Li; Ziyan Wei; Zhuanping Wang; Xuewen Kang

doi:10.1016/j.intimp.2024.112161

Bradykinin protects nucleus pulposus cells from tert-butyl hydroperoxide-induced damage and delays intervertebral disc degeneration

Int Immunopharmacol. 2024 May 9:134:112161. doi: 10.1016/j.intimp.2024.112161. Online ahead of print.

Authors

Xiaoming Qiu¹, Chongwen Ma², Zhangbin Luo², Yibao Zhang², Jihe Kang², Daxue Zhu², Zhaoheng Wang², Lei Li², Ziyan Wei², Zhuanping Wang³, Xuewen Kang⁴

Affiliations

¹ Department of Orthopedics, Lanzhou University Second Hospital, The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu 730000, China; Gansu provincial hospital of TCM (The First Affiliated Hospital of Gansu University of Chinese Medicine), Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou, Gansu 730000, China.
² Department of Orthopedics, Lanzhou University Second Hospital, The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu 730000, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou, Gansu 730000, China.
³ Department of endocrinology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, Gansu 730000, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou, Gansu 730000, China.
⁴ Department of Orthopedics, Lanzhou University Second Hospital, The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu 730000, China; Orthopaedics Key Laboratory of Gansu Province, Lanzhou, Gansu 730000, China. Electronic address: ery_kangxw@lzu.edu.cn.

PMID: 38728878
DOI: 10.1016/j.intimp.2024.112161

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.

Keywords: Bradykinin; Intervertebral disc degeneration; Kallikrein-kinin system; Nucleus pulposus cells; Oxidative stress; PI3K/AKT.