سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Luan, Jing, Wang, Qi, Zheng, Wei, He, Yongjin. (1403). The mTOR pathway is involved in the process of platelet-rich plasma improving intervertebral disc degeneration. , 28(3), 393-400. doi: 10.22038/ijbms.2024.79218.17163
Jing Luan; Qi Wang; Wei Zheng; Yongjin He. "The mTOR pathway is involved in the process of platelet-rich plasma improving intervertebral disc degeneration". , 28, 3, 1403, 393-400. doi: 10.22038/ijbms.2024.79218.17163
Luan, Jing, Wang, Qi, Zheng, Wei, He, Yongjin. (1403). 'The mTOR pathway is involved in the process of platelet-rich plasma improving intervertebral disc degeneration', , 28(3), pp. 393-400. doi: 10.22038/ijbms.2024.79218.17163
Luan, Jing, Wang, Qi, Zheng, Wei, He, Yongjin. The mTOR pathway is involved in the process of platelet-rich plasma improving intervertebral disc degeneration. , 1403; 28(3): 393-400. doi: 10.22038/ijbms.2024.79218.17163

The mTOR pathway is involved in the process of platelet-rich plasma improving intervertebral disc degeneration

Iranian Journal of Basic Medical Sciences
مقاله 15، دوره 28، شماره 3، خرداد 2025، صفحه 393-400    اصل مقاله (411.06 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2024.79218.17163
نویسندگان
Jing Luan1؛ Qi Wang2؛ Wei Zheng1؛ Yongjin He* 1
1Department of Pain, Tianjin First Central Hospital, Tianjin, 300110, China
2Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, 300110, China
چکیده
Objective(s): Platelet-rich plasma (PRP) contains multiple growth hormones that may stimulate tissue repair. We aimed to assess PRP’s efficacy and explore possible mechanisms using the intervertebral disc degeneration (IDD) model. 
Materials and Methods: A total of 48 male Sprague-Dawley (SD) rats were randomly divided into three groups: sham, IDD+PBS, and IDD+PRP (n=16, respectively). IL-1β (10 ng/ml) was used to establish a humanized IDD model in human lumbar nucleus pulposus (NP) tissues from 36 patients with degenerative disc disease. These NP cells were randomly divided into three groups: sham, IDD+PBS, and IDD+PRP (n=12, respectively). RT-PCR and western blot were used to detect the expression of aggrecan, collagen II, IL-1β, IL-6, TNF-α, Bcl-2, cleaved-Caspase 3, Bax and Akt/mTOR/p70S6K signaling pathway. A related assay kit was used to detect MDA, SOD, and GSH.
Results: PRP affected the expression of aggrecan, collagen II, IL-1β, IL-6, TNF-α, MDA, SOD, GSH, Bcl-2, cleaved-Caspase 3, and Bax in IDD rats. Compared with the IDD+PBS group, the expression of p-mTOR, p-p70/S6K, and p-Akt was much lower in the rat IDD+PRP group (P<0.05). Similarly, with PRP treatment in the humanized IDD model, the expression of p-mTOR, p-p70/S6K, and p-Akt was also inhibited.
Conclusion: PRP may be a potential therapy for IDD via the mTOR signaling pathway in regulating and affecting extracellular matrix degradation, inflammatory factors, oxidative stress, and apoptosis.
کلیدواژه‌ها
Akt/mTOR/p70S6K-signaling pathway؛ Apoptosis؛ Extracellular matrix- degradation؛ Inflammatory factors Intervertebral disc degeneration؛ Oxidative stress؛ Platelet-rich plasma
مراجع
1. Hartvigsen J, Hancock MJ, Kongsted A, Louw Q, Ferreira ML, Genevay S, et al. What low back pain is and why we need to pay attention. Lancet 2018; 391: 2356-2367.
2. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. 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; 392:1789-1858.
3. Wu A, March L, Zheng X, Huang J, Wang X, Zhao J, et al. Global low back pain prevalence and years lived with disability from 1990 to 2017: Estimates from the Global Burden of Disease Study 2017. Ann Transl Med 2020; 8: 299-312.
4. 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: 110660-110673.
5. Lai F, Kakudo N, Morimoto N, Taketani S, Hara T, Ogawa T, et al. Platelet-rich plasma enhances the proliferation of human adipose stem cells through multiple signaling pathways. Stem Cell Res Ther 2018; 9: 107-116.
6. Navone SE, Marfia G, Giannoni A, Beretta M, Guarnaccia L, Gualtierotti R, et al. Inflammatory mediators and signalling pathways controlling intervertebral disc degeneration. Histol Histopathol 2017; 32: 523-542.
7. Wang S, Sun J, Yang H, Zou W, Zheng B, Chen Y, et al. Profiling and bioinformatics analysis of differentially expressed circular RNAs in human intervertebral disc degeneration. Acta Biochim Biophys Sin (Shanghai) 2019; 51: 571-579.
8. Li H, Tian L, Li J, Li Y, Du L, Huo Z, et al. The Roles of circRNAs in intervertebral disc degeneration: inflammation, extracellular matrix metabolism, and apoptosis. Anal Cell Pathol (Amst) 2022; 2022: 9550499-9550507.
9. Davalli P, Mitic T, Caporali A, Lauriola A, D’Arca D. ROS, cell senescence, and novel molecular mechanisms in aging and age-related diseases. Oxid Med Cell Longev 2016; 2016: 3565127-3565144.
10. Heyde CE, Tschoeke SK, Hellmuth M, Hostmann A, Ertel W, Oberholzer A. Trauma induces apoptosis in human thoracolumbar intervertebral discs. BMC Clin Pathol 2006; 6: 5-13.
11. Wang H, Liu H, Zheng ZM, Zhang KB, Wang TP, Sribastav SS, et al. Role of death receptor, mitochondrial and endoplasmic reticulum pathways in different stages of degenerative human lumbar disc. Apoptosis 2011; 16: 990-1003.
12. Singh BN, Kumar D, Shankar S, Srivastava RK. Rottlerin induces autophagy which leads to apoptotic cell death through inhibition of PI3K/Akt/mTOR pathway in human pancreatic cancer stem cells. Biochem Pharmacol 2012; 84: 1154-1163.
13. Tu J, Li W, Li S, Liu W, Zhang Y, Wu X, et al. Sestrin-mediated inhibition of stress-induced intervertebral disc degradation through the enhancement of autophagy. Cell Physiol Biochem 2018; 45: 1940-1954.
14. Xu X, Hu J, Lu H. Histological observation of a gelatin sponge transplant loaded with bone marrow-derived mesenchymal stem cells combined with platelet-rich plasma in repairing an annulus defect. PLoS One 2017; 12: e0171500-171514.
15. Sanapati J, Manchikanti L, Atluri S, Jordan S, Albers SL, Pappolla MA, et al. Do regenerative medicine therapies provide long-term relief in chronic low back pain: A systematic review and metaanalysis. Pain Physician 2018; 21: 515-540.
16. Chang Y, Yang M, Ke S, Zhang Y, Xu G, Li Z. Effect of platelet-rich plasma on intervertebral disc degeneration in vivo and in vitro: A critical review. Oxid Med Cell Longev 2020; 2020: 8893819-8893828.
17. Moussa M, Lajeunesse D, Hilal G, El Atat O, Haykal G, Serhal R, et al. Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage. Exp Cell Res 2017; 352: 146-156.
18. Xu H, Xu F, Zhao J, Zhou C, Liu J. Platelet-rich plasma induces autophagy and promotes regeneration in human dental pulp cells. Front Bioeng Biotechnol 2021; 9: 659742-659751.
19. Shafik NM, El-Esawy RO, Mohamed DA, Deghidy EA, El-Deeb OS. Regenerative effects of glycyrrhizin and/or platelet rich plasma on type-II collagen induced arthritis: Targeting autophay machinery markers, inflammation and oxidative stress. Arch Biochem Biophys 2019; 675: 108095.
20. Jaumard NV, Leung J, Gokhale AJ, Guarino BB, Welch WC, Winkelstein BA. Relevant anatomic and morphological measurements of the rat spine: Considerations for rodent models of human spine trauma. Spine (Phila Pa 1976) 2015; 40: E1084-1092.
21. Rohanifar M, Clayton SW, Easson GWD, Patil DS, Lee F, Jing L, et al. Single cell RNA-sequence analyses reveal uniquely expressed genes and heterogeneous immune cell involvement in the rat model of intervertebral disc degeneration. Appl Sci (Basel) 2022; 12: 1-25.
22. Shiga Y, Orita S, Kubota G, Kamoda H, Yamashita M, Matsuura Y, et al. Freeze-dried platelet-rich plasma accelerates bone union with adequate rigidity in posterolateral lumbar fusion surgery model in rats. Sci Rep 2016; 6: 36715-36724.
23. Otagiri T, Shiga Y, Hozumi T, Matsuura Y, Tajiri I, Takayama N, et al. Combined effect of DBM, PRP, and bone marrow fluid on bone union in a rat posterolateral fusion model. Sci Rep 2023; 13: 15041-15049.
24. Dhurat R, Sukesh M. Principles and methods of preparation of platelet-rich plasma: A review and author’s perspective. J Cutan Aesthet Surg 2014; 7: 189-197.
25. Che H, Li J, Li Y, Ma C, Liu H, Qin J, et al. p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle. Elife 2020; 9: e52570-52582.
26. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402-408.
27. Chen J, Mei Z, Huang B, Zhang X, Liu J, Shan Z, et al. IL-6/YAP1/β-catenin signaling is involved in intervertebral disc degeneration. J Cell Physiol 2019; 234: 5964-5971.
28. Liang H, Yang X, Liu C, Sun Z, Wang X. Effect of NF-kB signaling pathway on the expression of MIF, TNF-α, IL-6 in the regulation of intervertebral disc degeneration. J Musculoskelet Neuronal Interact 2018; 18: 551-556.
29. Khan AN, Jacobsen HE, Khan J, Filippi CG, Levine M, Lehman RA, Jr, et al. Inflammatory biomarkers of low back pain and disc degeneration: a review. Ann N Y Acad Sci 2017; 1410: 68-84.
30. Saif DS, Hegazy NN, Zahran ES. Evaluating the efficacy of intra-articular injections of platelet rich plasma (PRP) in rheumatoid arthritis patients and its impact on inflammatory cytokines, disease activity and quality of life. Curr Rheumatol Rev 2021; 17: 232-241.
31. Liang H, Luo R, Li G, Zhang W, Song Y, Yang C. The proteolysis of ecm in intervertebral disc degeneration. Int J Mol Sci 2022; 23-37.
32. Vo NV, Hartman RA, Yurube T, Jacobs LJ, Sowa GA, Kang JD. Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration. Spine J 2013; 13: 331-341.
33. Xu H, Mei Q, He J, Liu G, Zhao J, Xu B. Correlation of matrix metalloproteinases-1 and tissue inhibitor of metalloproteinases-1 with patient age and grade of lumbar disk herniation. Cell Biochem Biophys 2014; 69: 439-444.
34. Sobajima S, Shimer AL, Chadderdon RC, Kompel JF, Kim JS, Gilbertson LG, et al. Quantitative analysis of gene expression in a rabbit model of intervertebral disc degeneration by real-time polymerase chain reaction. Spine J 2005; 5: 14-23.
35. Wei F, Zhong R, Zhou Z, Wang L, Pan X, Cui S, et al. In vivo experimental intervertebral disc degeneration induced by bleomycin in the rhesus monkey. BMC Musculoskelet Disord 2014; 15: 340-349.
36. Iwata M, Aikawa T, Hakozaki T, Arai K, Ochi H, Haro H, et al. Enhancement of Runx2 expression is potentially linked to β-catenin accumulation in canine intervertebral disc degeneration. J Cell Physiol 2015; 230: 180-190.
37. Ito M, Yurube T, Kakutani K, Maeno K, Takada T, Terashima Y, et al. Selective interference of mTORC1/RAPTOR protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism with Akt and autophagy induction. Osteoarthritis Cartilage 2017; 25: 2134-2146.
38. Cho H, Holt DC, 3rd, Smith R, Kim SJ, Gardocki RJ, Hasty KA. The effects of platelet-rich plasma on halting the progression in porcine intervertebral disc degeneration. Artif Organs 2016; 40:190-195.
39. Ragab GH, Halfaya FM, Ahmed OM, Abou El-Kheir W, Mahdi EA, Ali TM, et al. Platelet-rich plasma ameliorates monosodium iodoacetate-induced ankle osteoarthritis in the rat model via suppression of inflammation and oxidative stress. Evid Based Complement Alternat Med 2021; 2021: 6692432-6692444.
40. Yurube T, Hirata H, Kakutani K, Maeno K, Takada T, Zhang Z, et al. Notochordal cell disappearance and modes of apoptotic cell death in a rat tail static compression-induced disc degeneration model. Arthritis Res Ther 2014; 16: R31-41.
41. Tao SC, Yuan T, Rui BY, Zhu ZZ, Guo SC, Zhang CQ. Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway. Theranostics 2017; 7: 733-750.
42. Liu X, Wang L, Ma C, Wang G, Zhang Y, Sun S. Exosomes derived from platelet-rich plasma present a novel potential in alleviating knee osteoarthritis by promoting proliferation and inhibiting apoptosis of chondrocyte via Wnt/β-catenin signaling pathway. J Orthop Surg Res 2019; 14: 470-485.
43. Gruber HE, Hoelscher GL, Ingram JA, Bethea S, Hanley EN, Jr. Autophagy in the degenerating human intervertebral disc: In vivo molecular and morphological evidence, and induction of autophagy in cultured annulus cells exposed to proinflammatory cytokines-implications for disc degeneration. Spine (Phila Pa 1976) 2015; 40: 773-782.
44. Xu H, Xiong S, Wang H, Zhang M, Yu Y. The evidence and the possible significance of autophagy in degeneration model of human cervical end-plate cartilage. Exp Ther Med 2014; 7: 537-542.
45. Zoncu R, Efeyan A, Sabatini DM. mTOR: From growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2011; 12: 21-35.
46. Manning BD, Cantley LC. AKT/PKB signaling: Navigating downstream. Cell 2007; 129:1261-1274.
47. Yao M, Zhang J, Li Z, Bai X, Ma J, Li Y. Liraglutide protects nucleus pulposus cells against high-glucose induced apoptosis by activating PI3K/Akt/ mTOR/Caspase-3 and PI3K/Akt/GSK3β/Caspase-3 signaling pathways. Front Med (Lausanne) 2021; 8: 630962-630972.

آمار
تعداد مشاهده مقاله: 490
تعداد دریافت فایل اصل مقاله: 370