Xiao-Chuan Li, Wei Wang, Cheng Jiang, Yong-Long Chen, Jiong-Hui Chen, Zhen-Wu Zhang, Shao-Jian Luo, Rong-Chun Chen, Ping-Fan Mo, Ming-Liang Zhong, Jiang-You Shi, Chun-Ming Huang, Qin Chen, Yao-Hong Wu
Osteoarthritis and cartilage 2024 JanThis study aimed to explore the specific function of M2 macrophages in intervertebral disc degeneration (IDD). Intervertebral disc (IVD) samples from normal (n = 4) and IDD (n = 6) patients were collected, and the expression of M2-polarized macrophage marker, CD206, was investigated using immunohistochemical staining. Nucleus pulposus cells (NPCs) in a TNF-α environment were obtained, and a mouse caudal IVD puncture model was established. Mice with Rheb deletions, specifically in the myeloid lineage, were generated and subjected to surgery-induced IDD. IDD-induced damage and cell apoptosis were measured using histological scoring, X-ray imaging, immunohistochemical staining, and TdT-mediated dUTP nick end labeling (TUNEL) assay. Finally, mice and NPCs were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in IDD. Accumulation of CD206 in human and mouse IDD tissues was detected. Rheb deletion in the myeloid lineage (RheBcKO) increased the number of CD206+ M2-like macrophages (mean difference 18.6% [15.7-21.6%], P < 0.001), decreased cell apoptosis (mean difference -15.6% [-8.9 to 22.2%], P = 0.001) and attenuated the IDD process in the mouse IDD model. NPCs treated with Rspo2 displayed increased extracellular matrix catabolism and apoptosis; co-culture with a conditioned medium derived from RheBcKO mice inhibited these changes. Anti-Rspo2 treatment in the mouse caudal IVD puncture model exerted protective effects against IDD. Promoting CD206+ M2-like macrophages could reduce Rspo2 secretion, thereby alleviating experimental IDD. Rheb deletion may help M2-polarized macrophages accumulate and attenuate experimental IDD partially by inhibiting Rspo2 production. Hence, M2-polarized macrophages and Rspo2 may serve as therapeutic targets for IDD. Copyright © 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Xiao-Chuan Li, Wei Wang, Cheng Jiang, Yong-Long Chen, Jiong-Hui Chen, Zhen-Wu Zhang, Shao-Jian Luo, Rong-Chun Chen, Ping-Fan Mo, Ming-Liang Zhong, Jiang-You Shi, Chun-Ming Huang, Qin Chen, Yao-Hong Wu. CD206+ M2-like macrophages protect against intervertebral disc degeneration partially by targeting R-spondin-2. Osteoarthritis and cartilage. 2024 Jan;32(1):66-81
PMID: 37802465
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