Journal of Basic Research in Medical Sciences
J Basic Res Med Sci
Volume 13, Issue 1 (1-2026)
jbrms 2026, 13(1): 24-33 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Fatahi M, Behpoor N, Hosseinpour Delavar S, Farzaneghi P. Modulation of Brain Apoptotic Biomarkers by Aerobic Exercise and Mesenchymal Stem Cell Therapy in a Rat Model of Osteoarthritis. jbrms 2026; 13 (1) :24-33
URL: http://jbrms.medilam.ac.ir/article-1-988-en.html
URL: http://jbrms.medilam.ac.ir/article-1-988-en.html
Department of physical education and sport sciences, Razi University, Kermanshah, Iran , n_behpoor@yahoo.com
Abstract: (68 Views)
Introduction: Osteoarthritis is a degenerative joint disease causing irreversible structural and functional joint damage. Recent studies indicate it may also affect the brain by altering apoptotic biomarkers like Bcl-2 and BAX. This study aimed to assess the effects of aerobic exercise and mesenchymal stem cell (MSC) therapy, alone or combined, on brain apoptotic biomarkers in osteoarthritic rats.
Materials & Methods: Forty-eight male Wistar rats were divided into six groups: healthy control (G0), osteoarthritis (GI), osteoarthritis with saline (GII), MSC therapy (GIII), aerobic exercise (GIV), and combined therapy (GV). Osteoarthritis was surgically induced, and MSCs were injected intra-articularly. Aerobic exercise included treadmill running for eight weeks. After intervention, brain tissue was collected and Bcl-2 and BAX levels were measured using ELISA.
Results: Osteoarthritis significantly altered Bcl-2 and BAX levels in the brain compared to controls. MSC therapy, aerobic exercise, and their combination improved these biomarkers. Both individual treatments significantly reduced BAX and increased Bcl-2. The combined treatment improved biomarkers to a similar extent as individual therapies, with no statistically significant difference compared to MSC therapy (p = 0.992 for BAX, p = 0.732 for Bcl-2) or aerobic exercise (p = 1.000 for both BAX and Bcl-2).
Conclusion: This study shows that osteoarthritis can affect brain apoptotic pathways. Both MSC therapy and aerobic exercise effectively modulate these changes, suggesting their therapeutic potential. However, combining them did not enhance outcomes beyond individual treatments, highlighting the value of non-pharmacological interventions in osteoarthritis management.
Materials & Methods: Forty-eight male Wistar rats were divided into six groups: healthy control (G0), osteoarthritis (GI), osteoarthritis with saline (GII), MSC therapy (GIII), aerobic exercise (GIV), and combined therapy (GV). Osteoarthritis was surgically induced, and MSCs were injected intra-articularly. Aerobic exercise included treadmill running for eight weeks. After intervention, brain tissue was collected and Bcl-2 and BAX levels were measured using ELISA.
Results: Osteoarthritis significantly altered Bcl-2 and BAX levels in the brain compared to controls. MSC therapy, aerobic exercise, and their combination improved these biomarkers. Both individual treatments significantly reduced BAX and increased Bcl-2. The combined treatment improved biomarkers to a similar extent as individual therapies, with no statistically significant difference compared to MSC therapy (p = 0.992 for BAX, p = 0.732 for Bcl-2) or aerobic exercise (p = 1.000 for both BAX and Bcl-2).
Conclusion: This study shows that osteoarthritis can affect brain apoptotic pathways. Both MSC therapy and aerobic exercise effectively modulate these changes, suggesting their therapeutic potential. However, combining them did not enhance outcomes beyond individual treatments, highlighting the value of non-pharmacological interventions in osteoarthritis management.
Keywords: Bone remodeling, Brain-derived neurotrophic factor, Cartilage degeneration, Neuroinflammation, Neuronal plasticity, Oxidative stress, Synovitis
Type of Study: Research |
Subject:
Physiology
Received: 2025/07/4 | Accepted: 2025/08/31 | Published: 2026/01/4
Received: 2025/07/4 | Accepted: 2025/08/31 | Published: 2026/01/4
References
1. Buckwalter JA, Mankin HJ, Grodzinsky AJ. Articular cartilage and osteoarthritis. Instr Course Lect. 2005;54:465. doi.
2. Katz JN, Arant KR, Loeser RF. Diagnosis and treatment of hip and knee osteoarthritis: a review. JAMA. 2021;325(6):568-78. [DOI:10.1001/jama.2020.22171.]
3. Tudorachi NB, Totu EE, Fifere A, Ardeleanu V, Mocanu V, Mircea C, et al. The implication of reactive oxygen species and antioxidants in knee osteoarthritis. Antioxidants (Basel). 2021;10(6):985. [DOI:10.3390/antiox10060985.]
4. Zahan O-M, Serban O, Gherman C, Fodor D. The evaluation of oxidative stress in osteoarthritis. Med Pharm Rep. 2020;93(1):12. [DOI:10.15386/mpr-1422.]
5. Chaney S, Vergara R, Qiryaqoz Z, Suggs K, Akkouch A. The involvement of neutrophils in the pathophysiology and treatment of osteoarthritis. Biomedicines. 2022;10(7):1604. [DOI:10.3390/biomedicines10071604.]
6. Jenei-Lanzl Z, Meurer A, Zaucke F. Interleukin-1β signaling in osteoarthritis–chondrocytes in focus. Cell Signal. 2019;53:212-23. [DOI:10.1016/j.cellsig.2018.10.005.]
7. Rahman MM, Kopec JA, Cibere J, Goldsmith CH, Anis AH. The relationship between osteoarthritis and cardiovascular disease in a population health survey: a cross-sectional study. BMJ open. 2013;3(5):e002624. [DOI:10.1136/bmjopen-2013-002624.]
8. Piva SR, Susko AM, Khoja SS, Josbeno DA, Fitzgerald GK, Toledo FG. Links between osteoarthritis and diabetes: implications for management from a physical activity perspective. Clin Geriatr Med. 2014;31(1):67. http://doi.org/10.1016/j.cger.2014.08.019.
9. Belen E, Karaman O, Caliskan G, Atamaner O, Aslan O. Impaired aortic elastic properties in primary osteoarthritis. Vasc Med. 2016;24(1):70-7. [DOI:10.1177/1708538115584728.]
10. Kim HS, Shin J-S, Lee J, Lee YJ, Kim M-r, Bae Y-H, et al. Association between knee osteoarthritis, cardiovascular risk factors, and the Framingham Risk Score in South Koreans: a cross-sectional study. PLoS One. 2016;11(10):e0165325. [DOI:10.1371/journal.pone.0165325.]
11. Jalilian J, Behpoor N, Farzanegi P. Effect of Aerobic Training in Combination with Stem Cells on Inflammatory Biomarker Levels in the Heart Tissue of Rat Model of Osteoarthritis. J Ilam Univ Med Sci. 2020;28(1):12-26. http://doi.org/10.29252/sjimu.28.1.12.
12. Jalilian J, Behpour N, Hosseeinpoor Delavar S, Farzanegi P. The study of the effect of the aerobic training together with stem cells on the ievels of some of the apoptosis indices of the heart tissue of the male Wistar rats of osteoarthritis model. Jundishapur Sci Med J. 2020;18(6):585-602. http://doi.org/10.22118/jsmj.2019.200436.1813.
13. Parks EL, Gehal PY, Balikil MN, Katzl J, Schnitzerl TJ, Apkarianl AV. Brain activity for chronic knee osteoarthritis: dissociating evoked pain from spontaneous pain. Eur J pain. 2011;15(8):843. e1-. e14. [DOI:10.1016/j.ejpain.2010.12.007.]
14. Howard MA, Sanders D, Krause K, O'Muircheartaigh J, Fotopoulou A, Zelaya F, et al. Alterations in resting‐state regional cerebral blood flow demonstrate ongoing pain in osteoarthritis: An arterial spin‐labeled magnetic resonance imaging study. Arthrit Rheum. 2012;64(12):3936-46. [DOI:10.1002/art.37685.]
15. Suokas A, Walsh D, McWilliams D, Condon L, Moreton B, Wylde V, et al. Quantitative sensory testing in painful osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2012;20(10):1075-85. [DOI:10.1016/j.joca.2012.06.009.]
16. Wyndow N, Collins N, Vicenzino B, Tucker K, Crossley K. Is there a biomechanical link between patellofemoral pain and osteoarthritis? A narrative review. Sports Med. 2016;46(12):1797-808. http://doi.org/10.1007/s40279-016-0545-6.
17. Lluch Girbés E, Nijs J, Torres-Cueco R, López Cubas C. Pain treatment for patients with osteoarthritis and central sensitization. Phys Ther. 2013;93(6):842-51. [DOI:10.2522/ptj.20120253.]
18. Lluch E, Torres R, Nijs J, Van Oosterwijck J. Evidence for central sensitization in patients with osteoarthritis pain: a systematic literature review. Eur J pain. 2014;18(10):1367-75. [DOI:10.1002/j.1532-2149.2014.499.x.]
19. Lluch Girbés E, Dueñas L, Barbero M, Falla D, Baert IA, Meeus M, et al. Expanded distribution of pain as a sign of central sensitization in individuals with symptomatic knee osteoarthritis. Phys Ther. 2016;96(8):1196-207. [DOI:10.2522/ptj.20150492.]
20. Lluch E, Nijs J, Courtney CA, Rebbeck T, Wylde V, Baert I, et al. Clinical descriptors for the recognition of central sensitization pain in patients with knee osteoarthritis. Disabil Rehabil. 2018;40(23):2836-45. [DOI:10.1080/09638288.2017.1358770.]
21. Barroso J, Wakaizumi K, Reis AM, Baliki M, Schnitzer TJ, Galhardo V, et al. Reorganization of functional brain network architecture in chronic osteoarthritis pain. Hum Brain Mapp. 2021;42(4):1206-22. [DOI:10.1002/hbm.25287.]
22. Fatahi M, Behpoor N, Hosseinpourdelavar S, Farzaneghi P. The effect of aerobic exercise combined with bone marrow mesenchymal stem cells on inflammatory biomarkers levels of the brain in a model of osteoarthritic rat. J Basic Res Med Sci. 2021;8(3):32-9. doi.
23. Kristjánsson B, Honsawek S. Current perspectives in mesenchymal stem cell therapies for osteoarthritis. Stem Cells Int. 2014;2014(1):194318. [DOI:10.1155/2014/194318.]
24. Furuoka H, Endo K, Sekiya I. Mesenchymal stem cells in synovial fluid increase in number in response to synovitis and display more tissue-reparative phenotypes in osteoarthritis. Stem Cell Res Ther. 2023;14(1):244. [DOI:10.1186/s13287-023-03487-1.]
25. Smith JK. Exercise as an adjuvant to cartilage regeneration therapy. Int J Mol Sci. 2020;21(24):9471. [DOI:10.3390/ijms21249471.]
26. Zhao Y, Liu B, Liu C-j. Establishment of a surgically-induced model in mice to investigate the protective role of progranulin in osteoarthritis. J Vis Exp. 2014(84):50924. http://doi.org/10.3791/50924.
27. Li M, Luo X, Lv X, Liu V, Zhao G, Zhang X, et al. In vivo human adipose-derived mesenchymal stem cell tracking after intra-articular delivery in a rat osteoarthritis model. Stem Cell Res Ther. 2016;7(1):160. [DOI:10.1186/s13287-016-0420-2.]
28. Stark AM, Hugo H-H, Tscheslog H, Mehdorn HM. p53, BCL-2 and BAX in non-small cell lung cancer brain metastases: a comparison of real-time RT-PCR, ELISA and immunohistochemical techniques. Neurol Res. 2007;29(5):435-40. [DOI:10.1179/016164107X165282.]
29. Siddall PJ, Stanwell P, Woodhouse A, Somorjai RL, Dolenko B, Nikulin A, et al. Magnetic resonance spectroscopy detects biochemical changes in the brain associated with chronic low back pain: a preliminary report. Anesth Analg. 2006;102(4):1164-8. http://doi.org/10.1213/01.ane.0000198333.22687.a6.
30. Saab CY. Pain-related changes in the brain: diagnostic and therapeutic potentials. Trends Neurosci. 2012;35(10):629-37. http://doi.org/10.1016/j.tins.2012.06.002.
31. Singh R, Letai A, Sarosiek K. Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol. 2019;20(3):175-93. [DOI:10.1038/s41580-018-0089-8.]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |