Sympathetic Neurotransmitter, VIP, Delays Intervertebral Disc Degeneration via FGF18/FGFR2-Mediated Activation of Akt Signaling Pathway.

Autor: Sun K; Department of Orthopedic Surgery, Changzheng Hospital, Navy Medical University, No.415 Fengyang Road, Shanghai, 200003, China.; Department of Orthopedics, Naval Medical Center of PLA, Navy Medical University, No.338 Western HuaiHai Road, Shanghai, 200003, China., Sun J; Department of Orthopedics, Naval Medical Center of PLA, Navy Medical University, No.338 Western HuaiHai Road, Shanghai, 200003, China., Yan C; Department of Orthopedic Surgery, Changzheng Hospital, Navy Medical University, No.415 Fengyang Road, Shanghai, 200003, China., Sun J; Department of Orthopedic Surgery, Changzheng Hospital, Navy Medical University, No.415 Fengyang Road, Shanghai, 200003, China., Xu X; Department of Orthopedic Surgery, Changzheng Hospital, Navy Medical University, No.415 Fengyang Road, Shanghai, 200003, China., Shi J; Department of Orthopedic Surgery, Changzheng Hospital, Navy Medical University, No.415 Fengyang Road, Shanghai, 200003, China.
Jazyk: angličtina
Zdroj: Advanced biology [Adv Biol (Weinh)] 2024 Mar; Vol. 8 (3), pp. e2300250. Date of Electronic Publication: 2023 Dec 04.
DOI: 10.1002/adbi.202300250
Abstrakt: Neuromodulation-related intervertebral disc degeneration (IVDD) is a novel IVDD pattern and are proposed recently. However, the mechanistic basis of neuromodulation and intervertebral disc (IVD) homeostasis remains unclear. Here, this study aimed to investigate the expression of postganglionic sympathetic nerve fiber-derived vasoactive intestinal peptide (VIP) system in human IVD tissue, and to assess the role of VIP-related neuromodulation in IVDD. Patient samples and in vitro cell experiments showed that the expression of receptors for VIP is negatively correlated with the severity of IVDD, and the administration of exogenous VIP can ameliorate interleukin 1β-induced nucleus pulposus (NP) cell apoptosis and inflammation. Further mRNA-seq analysis revealed that fibroblast growth factor 18- (FGF18)-mediated activation of V-akt murine thymoma viral oncogene homolog signaling pathway is involved in the protective effects of VIP on inflammation-induced NP cell degeneration. Further analysis identified VIP via its receptor vasoactive intestinal peptide receptor 2 can directly result in decreased expression of miR-15a-5p, which targeted FGF18. Finally, in vivo mice lumbar IVDD model confirmed that focally exogenous administration of VIP can effectively ameliorated the progression of IVDD, as shown by the radiological and histological analysis. In conclusion, these results indicated that sympathetic neurotransmitter, VIP, delayed IVDD via FGF18/FGFR2-mediated activation of V-akt murine thymoma viral oncogene homolog signaling pathway, which will broaden the horizon concerning how the neuromodulation correlates with IVDD and shed new light on novel therapeutical alternatives to IVDD.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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