D‑mannose alleviates intervertebral disc degeneration through glutamine metabolism  

作　　者：Zheng-Lin Dong Xin Jiao Zeng-Guang Wang Kai Yuan Yi-Qi Yang Yao Wang Yun-Tao Li Tian-Chang Wang Tian-You Kan Jian Wang Hai-Rong Tao 

机构地区：[1]Department of Orthopedics,Shanghai Key Laboratory of Orthopedic Implant,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China [2]School of Medicine,Shanghai University,Shanghai 200444,China

出　　处：《Military Medical Research》2025年第3期313-338,共26页军事医学研究(英文版)

基　　金：supported by the National Key Research and Development Program of China(2020YFB1711505).

摘　　要：Background:Intervertebral disc degeneration(IVDD)is a multifaceted condition characterized by heterogeneity,wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus(NP)cells plays a central role.Presently,the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes.D-mannose(referred to as mannose)has demonstrated anti-catabolic properties in various diseases.Nevertheless,its therapeutic potential in IVDD has yet to be explored.Methods:The study began with optimizing the mannose concentration for restoring NP cells.Transcriptomic analyses were employed to identify the mediators influenced by mannose,with the thioredoxin-interacting protein(TXNIP)gene showing the most significant differences.Subsequently,small interfering RNA(siRNA)technology was used to demonstrate that TXNIP is the key gene through which mannose exerts its effects.Techniques such as colocalization analysis,molecular docking,and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP.To elucidate the mechanism of action of mannose,metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose.Next,various methods,including integrated omics data and the Gene Expression Omnibus(GEO)database,were used to validate the one-way pathway through which TXNIP regulates glutamine.Finally,the therapeutic effect of mannose on IVDD was validated,elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats.Results:In both in vivo and in vitro experiments,it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism.From a mechanistic standpoint,it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein(MondoA),resulting in the upregulation of TXNIP.This upregu

关 键 词：D-MANNOSE Intervertebral disc degeneration(IVDD) Thioredoxin-interacting protein(TXNIP) GLUTAMINE 

分 类 号：R681.5[医药卫生—骨科学]