Carapetis JR, Dadi AF. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global burden of disease study 2016. Lancet. 2017;390:1211–59.
Google Scholar
James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, Abbastabar H, Abd-Allah F, Abdela J, Abdelalim A, Abdollahpour I. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1789–858.
Google Scholar
Francisco V, Pino J, González-Gay M, Lago F, Karppinen J, Tervonen O, Mobasheri A, Gualillo O. A new immunometabolic perspective of intervertebral disc degeneration. Nat Rev Rheumatol. 2022;18:47–60.
Google Scholar
Ruiz-Fernández C, Francisco V, Pino J, Mera A, González-Gay MA, Gómez R, Lago F, Gualillo O. Molecular relationships among obesity, inflammation and intervertebral disc degeneration: are adipokines the common link? Int J Mol Sci. 2019;20:2030.
Google Scholar
Karademir M, Eser O, Karavelioglu E. Adolescent lumbar disc herniation: Impact, diagnosis, and treatment. J Back Musculoskelet Rehabil. 2017;30:347–52.
Google Scholar
Pietilä TA, Stendel R, Kombos T, Ramsbacher J, Schulte T, Brock M. Lumbar disc herniation in patients up to 25 years of age. Neurol Med Chir (Tokyo). 2001;41:340–4.
Google Scholar
Lee JY, Ernestus RI, Schröder R, Klug N. Histological study of lumbar intervertebral disc herniation in adolescents. Acta Neurochir (Wien). 2000;142:1107–10.
Google Scholar
MacLean JJ, Lee CR, Grad S, Ito K, Alini M, Iatridis JC. Effects of immobilization and dynamic compression on intervertebral disc cell gene expression in vivo. Spine (Phila Pa 1976). 2003;28:973–81.
Google Scholar
Takada T, Nishida K, Maeno K, Kakutani K, Yurube T, Doita M, Kurosaka M. Intervertebral disc and macrophage interaction induces mechanical hyperalgesia and cytokine production in a herniated disc model in rats. Arthritis Rheum. 2012;64:2601–10.
Google Scholar
Wang J, Tian Y, Phillips KL, Chiverton N, Haddock G, Bunning RA, Cross AK, Shapiro IM, Le Maitre CL, Risbud MV. Tumor necrosis factor α- and interleukin-1β-dependent induction of CCL3 expression by nucleus pulposus cells promotes macrophage migration through CCR1. Arthritis Rheum. 2013;65:832–42.
Google Scholar
Nerlich AG, Weiler C, Zipperer J, Narozny M, Boos N. Immunolocalization of phagocytic cells in normal and degenerated intervertebral discs. Spine. 2002;27:2484–90.
Google Scholar
Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012;122:787–95.
Google Scholar
Ni L, Zheng Y, Gong T, Xiu C, Li K, Saijilafu, Li B, Yang H, Chen J. Proinflammatory macrophages promote degenerative phenotypes in rat nucleus pulpous cells partly through ERK and JNK signaling. J Cell Physiol. 2019;234:5362–71.
Google Scholar
Dou X, Luo Q, Xie L, Zhou X, Song C, Liu M, Liu X, Ma Y, Liu X. Medical Prospect of melatonin in the intervertebral disc degeneration through inhibiting M1-type macrophage polarization via SIRT1/notch signaling pathway. Biomedicines. 2023;11:1615.
Google Scholar
Zhao F, Guo Z, Hou F, Fan W, Wu B, Qian Z. Magnoflorine alleviates “M1” polarized macrophage-induced intervertebral disc degeneration through repressing the HMGB1/Myd88/NF-κB pathway and NLRP3 inflammasome. Front Pharmacol. 2021;12: 701087.
Google Scholar
Cocucci E, Meldolesi J. Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends Cell Biol. 2015;25:364–72.
Google Scholar
Simons M, Raposo G. Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol. 2009;21:575–81.
Google Scholar
Meng QF, Tai W, Tian M, Zhuang X, Pan Y, Lai J, Xu Y, Xu Z, Li M, Zhao G, et al. Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates. Sci Adv. 2023;9:eadg3277.
Google Scholar
Wu R, Gao W, Yao K, Ge J. Roles of exosomes derived from immune cells in cardiovascular diseases. Front Immunol. 2019;10:648.
Google Scholar
Jiang H, Zhou L, Shen N, Ning X, Wu D, Jiang K, Huang X. M1 macrophage-derived exosomes and their key molecule lncRNA HOTTIP suppress head and neck squamous cell carcinoma progression by upregulating the TLR5/NF-κB pathway. Cell Death Dis. 2022;13:183.
Google Scholar
Liu S, Chen J, Shi J, Zhou W, Wang L, Fang W, Zhong Y, Chen X, Chen Y, Sabri A, Liu S. M1-like macrophage-derived exosomes suppress angiogenesis and exacerbate cardiac dysfunction in a myocardial infarction microenvironment. Basic Res Cardiol. 2020;115:22.
Google Scholar
Sharma N, Akkoyunlu M, Rabin RL. Macrophages-common culprit in obesity and asthma. Allergy. 2018;73:1196–205.
Google Scholar
Du R, Chen S, Han C, He Z, Pei H, Yang Y. M1 intestinal macrophages-derived exosomes promote colitis progression and mucosal barrier injury. Aging (Albany NY). 2024;16:5703–10.
Google Scholar
Wang P, Wang H, Huang Q, Peng C, Yao L, Chen H, Qiu Z, Wu Y, Wang L, Chen W. Exosomes from M1-polarized macrophages enhance paclitaxel antitumor activity by activating macrophages-mediated inflammation. Theranostics. 2019;9:1714–27.
Google Scholar
Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005;120:513–22.
Google Scholar
Coppé JP, Desprez PY, Krtolica A, Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010;5:99–118.
Google Scholar
Wang F, Cai F, Shi R, Wang XH, Wu XT. Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration. Osteoarthritis Cartilage. 2016;24:398–408.
Google Scholar
Lin J, Du J, Wu X, Xu C, Liu J, Jiang L, Cheng X, Ge G, Chen L, Pang Q, et al. SIRT3 mitigates intervertebral disc degeneration by delaying oxidative stress-induced senescence of nucleus pulposus cells. J Cell Physiol. 2021;236:6441–56.
Google Scholar
Du J, Xu M, Kong F, Zhu P, Mao Y, Liu Y, Zhou H, Dong Z, Yu Z, Du T, et al. CB2R attenuates intervertebral disc degeneration by delaying nucleus pulposus cell senescence through AMPK/GSK3β pathway. Aging Dis. 2022;13:552–67.
Google Scholar
Yu S, Cheng Y, Li B, Xue J, Yin Y, Gao J, Gong Z, Wang J, Mu Y. M1 macrophages accelerate renal glomerular endothelial cell senescence through reactive oxygen species accumulation in streptozotocin-induced diabetic mice. Int Immunopharmacol. 2020;81: 106294.
Google Scholar
Yuan D, Zhao Y, Banks WA, Bullock KM, Haney M, Batrakova E, Kabanov AV. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain. Biomaterials. 2017;142:1–12.
Google Scholar
Zhou YL, Chen G, Bi DC, Chen X. Short-term clinical efficacy of percutaneous transforaminal endoscopic discectomy in treating young patients with lumbar disc herniation. J Orthop Surg Res. 2018;13:61.
Google Scholar
Hu B, Lv X, Wei L, Wang Y, Zheng G, Yang C, Zang F, Wang J, Li J, Wu X, et al. Sensory nerve maintains intervertebral disc extracellular matrix homeostasis via CGRP/CHSY1 axis. Adv Sci (Weinh). 2022;9: e2202620.
Google Scholar
Guo M, Wang J, Zhao Y, Feng Y, Han S, Dong Q, Cui M, Tieu K. Microglial exosomes facilitate α-synuclein transmission in Parkinson’s disease. Brain. 2020;143:1476–97.
Google Scholar
Salminen A, Kauppinen A, Kaarniranta K. Emerging role of NF-κB signaling in the induction of senescence-associated secretory phenotype (SASP). Cell Signal. 2012;24:835–45.
Google Scholar
Wu J, Chen Y, Liao Z, Liu H, Zhang S, Zhong D, Qiu X, Chen T, Su D, Ke X, et al. Self-amplifying loop of NF-κB and periostin initiated by PIEZO1 accelerates mechano-induced senescence of nucleus pulposus cells and intervertebral disc degeneration. Mol Ther. 2022;30:3241–56.
Google Scholar
Segar AH, Fairbank JCT, Urban J. Leptin and the intervertebral disc: a biochemical link exists between obesity, intervertebral disc degeneration and low back pain-an in vitro study in a bovine model. Eur Spine J. 2019;28:214–23.
Google Scholar
Martínez-Lage JF, Fernández Cornejo V, López F, Poza M. Lumbar disc herniation in early childhood: case report and literature review. Childs Nerv Syst. 2003;19:258–60.
Google Scholar
Priyadarshani P, Li Y, Yao L. Advances in biological therapy for nucleus pulposus regeneration. Osteoarthritis Cartilage. 2016;24:206–12.
Google Scholar
Wang Y, Che M, Xin J, Zheng Z, Li J, Zhang S. The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomed Pharmacother. 2020;131: 110660.
Google Scholar
Molinos M, Almeida CR, Caldeira J, Cunha C, Gonçalves RM, Barbosa MA. Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface. 2015;12:20150429.
Google Scholar
Ma Z, Tang P, Dong W, Lu Y, Tan B, Zhou N, Hao J, Shen J, Hu Z. SIRT1 alleviates IL-1β induced nucleus pulposus cells pyroptosis via mitophagy in intervertebral disc degeneration. Int Immunopharmacol. 2022;107: 108671.
Google Scholar
Rose-John S. Interleukin-6 family cytokines. Cold Spring Harb Perspect Biol. 2018;10: a028415.
Google Scholar
Wang SS, Zhang W, Zhang YQ, Zhao Y, Liu Y, Li JK, Zhang HX, Cheng L, Nie L. IL-17A enhances ADAMTS-7 expression through regulation of TNF-α in human nucleus pulposus cells. J Mol Histol. 2015;46:475–83.
Google Scholar
Sun Y, Li J, Xie X, Gu F, Sui Z, Zhang K, Yu T. Macrophage-osteoclast associations: origin, polarization, and subgroups. Front Immunol. 2021;12: 778078.
Google Scholar
Liu YC, Zou XB, Chai YF, Yao YM. Macrophage polarization in inflammatory diseases. Int J Biol Sci. 2014;10:520–9.
Google Scholar
Tu J, Li W, Yang S, Yang P, Yan Q, Wang S, Lai K, Bai X, Wu C, Ding W, et al. Single-cell transcriptome profiling reveals multicellular ecosystem of nucleus pulposus during degeneration progression. Adv Sci (Weinh). 2022;9: e2103631.
Google Scholar
Li W, Zhao Y, Wang Y, He Z, Zhang L, Yuan B, Li C, Luo Z, Gao B, Yan M. Deciphering the sequential changes of monocytes/macrophages in the progression of IDD with longitudinal approach using single-cell transcriptome. Front Immunol. 2023;14:1090637.
Google Scholar
Schreiber A, Rousselle A, Klocke J, Bachmann S, Popovic S, Bontscho J, Schmidt-Ott KM, Siffrin V, Jerke U, Ashraf MI, et al. Neutrophil gelatinase-associated lipocalin protects from ANCA-induced GN by inhibiting T(H)17 immunity. J Am Soc Nephrol. 2020;31:1569–84.
Google Scholar
Francisco V, Ait Eldjoudi D, González-Rodríguez M, Ruiz-Fernández C, Cordero-Barreal A, Marques P, Sanz MJ, Real JT, Lago F, Pino J, et al. Metabolomic signature and molecular profile of normal and degenerated human intervertebral disc cells. Spine J. 2023;23:1549–62.
Google Scholar
Gupta K, Shukla M, Cowland JB, Malemud CJ, Haqqi TM. Neutrophil gelatinase-associated lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9. Arthritis Rheum. 2007;56:3326–35.
Google Scholar
Kao TH, Peng YJ, Salter DM, Lee HS. Nerve growth factor increases MMP9 activity in annulus fibrosus cells by upregulating lipocalin 2 expression. Eur Spine J. 2015;24:1959–68.
Google Scholar
Gupta U, Ghosh S, Wallace CT, Shang P, Xin Y, Nair AP, Yazdankhah M, Strizhakova A, Ross MA, Liu H, et al. Increased LCN2 (lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD. Autophagy. 2023;19:92–111.
Google Scholar
Xia Y, Ge G, Xiao H, Wu M, Wang T, Gu C, Yang H, Geng D. REPIN1 regulates iron metabolism and osteoblast apoptosis in osteoporosis. Cell Death Dis. 2023;14:631.
Google Scholar
Jiang SY, Tian T, Yao H, Xia XM, Wang C, Cao L, Hu G, Du RH, Lu M. The cGAS-STING-YY1 axis accelerates progression of neurodegeneration in a mouse model of Parkinson’s disease via LCN2-dependent astrocyte senescence. Cell Death Differ. 2023;30:2280–92.
Google Scholar
Bassères DS, Baldwin AS. Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene. 2006;25:6817–30.
Google Scholar
Zhongyi S, Sai Z, Chao L, Jiwei T. Effects of nuclear factor kappa B signaling pathway in human intervertebral disc degeneration. Spine(Phila Pa 1976). 2015;40:224–32.
Google Scholar
Li P, Gan Y, Xu Y, Wang L, Ouyang B, Zhang C, Luo L, Zhao C, Zhou Q. 17beta-estradiol attenuates TNF-α-induced premature senescence of nucleus pulposus cells through regulating the ROS/NF-κB pathway. Int J Biol Sci. 2017;13:145–56.
Google Scholar
Feng M, Feng J, Chen W, Wang W, Wu X, Zhang J, Xu F, Lai M. Lipocalin2 suppresses metastasis of colorectal cancer by attenuating NF-κB-dependent activation of snail and epithelial mesenchymal transition. Mol Cancer. 2016;15:77.
Google Scholar
Huang Z, Zhang Y, Li H, Zhou Y, Zhang Q, Chen R, Jin T, Hu K, Li S, Wang Y, et al. Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3. Cell Death Dis. 2019;10:936.
Google Scholar
Kamali A, Ziadlou R, Lang G, Pfannkuche J, Cui S, Li Z, Richards RG, Alini M, Grad S. Small molecule-based treatment approaches for intervertebral disc degeneration: current options and future directions. Theranostics. 2021;11:27–47.
Google Scholar
Bermudez-Lekerika P, Crump KB, Tseranidou S, Nüesch A, Kanelis E, Alminnawi A, Baumgartner L, Muñoz-Moya E, Compte R, Gualdi F, et al. Immuno-modulatory effects of intervertebral disc cells. Front Cell Dev Biol. 2022;10: 924692.
Google Scholar
Sousa-Valente J, Brain SD. A historical perspective on the role of sensory nerves in neurogenic inflammation. Semin Immunopathol. 2018;40:229–36.
Google Scholar
Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367:eaau6977.
Google Scholar
Lee YH, Park HK, Auh QS, Nah H, Lee JS, Moon HJ, Heo DN, Kim IS, Kwon IK. Emerging potential of exosomes in regenerative medicine for temporomandibular joint osteoarthritis. Int J Mol Sci. 2020;21:1541.
Google Scholar
Noonin C, Thongboonkerd V. Exosome-inflammasome crosstalk and their roles in inflammatory responses. Theranostics. 2021;11:4436–51.
Google Scholar
Lai J, Pan Q, Chen G, Liu Y, Chen C, Pan Y, Liu L, Zeng B, Yu L, Xu Y, et al. Triple hybrid cellular nanovesicles promote cardiac repair after ischemic reperfusion. ACS Nano. 2024;18:4443–55.
Google Scholar
Tan D, Zhu W, Liu L, Pan Y, Xu Y, Huang Q, Li L, Rao L. In situ formed scaffold with royal jelly-derived extracellular vesicles for wound healing. Theranostics. 2023;13:2811–24.
Google Scholar
Liao Z, Luo R, Li G, Song Y, Zhan S, Zhao K, Hua W, Zhang Y, Wu X, Yang C. Exosomes from mesenchymal stem cells modulate endoplasmic reticulum stress to protect against nucleus pulposus cell death and ameliorate intervertebral disc degeneration in vivo. Theranostics. 2019;9:4084–100.
Google Scholar
Luo L, Jian X, Sun H, Qin J, Wang Y, Zhang J, Shen Z, Yang D, Li C, Zhao P, et al. Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy. Stem Cells. 2021;39:467–81.
Google Scholar