Verification of pain-related neuromodulation mechanisms of icariin in knee osteoarthritis

被引:23
作者
Li, Xihai [1 ,2 ]
Xu, Yunteng [2 ,3 ]
Li, Hui [2 ,3 ]
Jia, Liangliang [2 ,3 ]
Wang, Jie [4 ,5 ]
Liang, Shengxiang [6 ,7 ]
Cai, Aoling [4 ,5 ]
Tan, Xue [2 ,3 ]
Wang, Lili [2 ,3 ]
Wang, Xiaoning [1 ,2 ]
Huang, Yanfeng [2 ,3 ]
Tao, Enxiang [8 ]
Ye, Hongzhi [2 ,3 ]
Asakawa, Tetsuya [8 ,9 ]
机构
[1] Fujian Univ Tradit Chinese Med, Coll Integrat Med, Fuzhou 350122, Peoples R China
[2] Fujian Key Lab Integrat Med Geriatr, Fuzhou 350122, Peoples R China
[3] Fujian Univ Tradit Chinese Med, Acad Integrat Med, Fuzhou 350122, Fujian, Peoples R China
[4] Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Peoples R China
[5] Innovat Acad Precis Measurement Sci, Wuhan 430071, Peoples R China
[6] Fujian Univ Tradit Chinese Med, Natl Local Joint Engn Res Ctr Rehabil Med Technol, Fuzhou 350122, Peoples R China
[7] Fujian Univ Tradit Chinese Med, Rehabil Ind Inst, Fuzhou 350122, Peoples R China
[8] Sun Yat Sen Univ, Affiliated Hosp 8, Dept Neurol, Shennanzhong Rd 3025, Shenzhen 518033, Guangdong, Peoples R China
[9] Fujian Univ Tradit Chinese Med, Res Base Tradit Chinese Med Syndrome, Fuzhou 350122, Peoples R China
关键词
Icariin; Knee osteoarthritis; Neuropeptides; Functional magnetic resonance imaging; Virus retrograde tracing; pain-related genesc; GENE-RELATED PEPTIDE; SYNOVIAL-FLUID; SUBSTANCE-P; NEUROPATHIC PAIN; NEUROPEPTIDE-Y; RAT MODEL; EXPRESSION; JOINT; IMMUNOREACTIVITY; NEUROKININ;
D O I
10.1016/j.biopha.2021.112259
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Knee osteoarthritis (KOA) is a common disease with no specific treatment. Icariin (ICA) is considered an agent for KOA. This study aimed to confirm the pain-related neuromodulation mechanisms of ICA on KOA. Three experiments were designed: (1) verifying the therapeutic effects of ICA in vivo and in vitro, (2) exploring the potential pain-related neuromodulation pathways involved in ICA treatment by functional magnetic resonance imaging (fMRI) and virus retrograde tracing (VRT) and (3) confirming the pain-related targets by tandem mass tag (TMT)-based quantitative proteomics and bioinformatic analyses. Experiment 1 verified the efficacy of ICA in OA animal and cell models. Experiment 2 found a series of brain regions associated with KOA reversed by ICA treatment, indicating that a pain-related hypothalamic-mediated neuromodulation pathway and an endocannabinoid (EC)-related pathway contribute to ICA mechanisms. Experiment 3 explored and confirmed four pain-related genes involved in KOA and ICA treatment. We confirmed the key role of pain-related neuromodulation mechanisms in ICA treatment associated with its analgesic effect. Our findings contribute to considering ICA as a novel therapy for KOA.
引用
收藏
页数:14
相关论文
共 39 条
[1]   The brain-joint axis in osteoarthritis: nerves, circadian clocks and beyond [J].
Berenbaum, Francis ;
Meng, Qing-Jun .
NATURE REVIEWS RHEUMATOLOGY, 2016, 12 (09) :508-516
[2]  
Bian Qin, 2012, Front Biosci (Elite Ed), V4, P1224
[3]   BILATERAL CHANGES OF SUBSTANCE-P-LIKE, NEUROKININ-A-LIKE, CALCITONIN GENE-RELATED PEPTIDE-LIKE AND NEUROPEPTIDE-Y-LIKE IMMUNOREACTIVITY IN RAT KNEE-JOINT SYNOVIAL-FLUID DURING ACUTE MONOARTHRITIS [J].
BILEVICIUTE, I ;
LUNDEBERG, T ;
EKBLOM, A ;
THEODORSSON, E .
NEUROSCIENCE LETTERS, 1993, 153 (01) :37-40
[4]   CALCITONIN GENE-RELATED PEPTIDE, SUBSTANCE-P AND GAP-43/B-50 IMMUNOREACTIVITY IN THE NORMAL AND ARTHROTIC KNEE-JOINT OF THE MOUSE [J].
BUMA, P ;
VERSCHUREN, C ;
VERSLEYEN, D ;
VANDERKRAAN, P ;
OESTREICHER, AB .
HISTOCHEMISTRY, 1992, 98 (05) :327-339
[5]   Isolation and Characterisation of a Recombinant Antibody Fragment That Binds NCAM1-Expressing Intervertebral Disc Cells [J].
Cunningham, Claire ;
Srivastava, Akshay ;
Collin, Estelle ;
Grad, Sibylle ;
Alini, Mauro ;
Pandit, Abhay ;
Wall, J. Gerard .
PLOS ONE, 2013, 8 (12)
[6]   Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease [J].
Delgado, M ;
Abad, C ;
Martinez, C ;
Laceta, J ;
Gomariz, RP .
NATURE MEDICINE, 2001, 7 (05) :563-568
[7]   Do Neuroendocrine Peptides and Their Receptors Qualify as Novel Therapeutic Targets in Osteoarthritis? [J].
Graessel, Susanne ;
Muschter, Dominique .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (02)
[8]   Neuronal control of bone and muscle [J].
Houweling, Peter ;
Kulkarni, Rishikesh N. ;
Baldock, Paul A. .
BONE, 2015, 80 :95-100
[9]   Nogo-A promotes inflammatory heat hyperalgesia by maintaining TRPV-1 function in the rat dorsal root ganglion neuron [J].
Hu, Fang ;
Liu, Huai-Cun ;
Su, Dong-Qiang ;
Chen, Hai-Jing ;
Chan, Sun-On ;
Wang, Yun ;
Wang, Jun .
FASEB JOURNAL, 2019, 33 (01) :668-682
[10]   Icariin Protects against Glucocorticoid-Induced Osteonecrosis of the Femoral Head in Rats [J].
Huang, Zengfa ;
Cheng, Cheng ;
Cao, Beibei ;
Wang, Jing ;
Wei, Hui ;
Liu, Xianzhe ;
Han, Yu ;
Yang, Shuhua ;
Wang, Xiang .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2018, 47 (02) :694-706