en Physiology Physiology پژوهشي Research <span style="font-size:9pt"><span minion="" pro="" style="font-family:"><b>Introduction</b>: 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.</span></span><br> <span style="font-size:9pt"><span minion="" pro="" style="font-family:"><b>Materials & Methods</b><b><span style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">: </span></span></b>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.<span lang="FA" dir="RTL" style="font-family:"Times New Roman",serif"></span></span></span><br> <span style="font-size:9pt"><span minion="" pro="" style="font-family:"><b>Results</b><b><span style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">: &nbsp;</span></span></b>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).</span></span><br> <span style="font-size:9pt"><span minion="" pro="" style="font-family:"><b>Conclusion</b><b><span style="font-size:11.0pt"><span new="" roman="" style="font-family:" times="">: &nbsp;</span></span></b>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.</span></span><br> &nbsp; Bone remodeling, Brain-derived neurotrophic factor, Cartilage degeneration, Neuroinflammation, Neuronal plasticity, Oxidative stress, Synovitis 24 33 http://jbrms.medilam.ac.ir/browse.php?a_code=A-10-504-15&slc_lang=en&sid=1 Mohamad Fatahi mohamadfatahi02@gmail.com 10031947532846008119 10031947532846008119 No Department of Exercise Physiology, Ker.C, Islamic Azad University, Kermanshah, Iran Naser Behpoor n_behpoor@yahoo.com 10031947532846008120 10031947532846008120 Yes Department of physical education and sport sciences, Razi University, Kermanshah, Iran Sedigheh Hosseinpour Delavar delavar2009@yahoo.com 10031947532846008121 10031947532846008121 No Department of Exercise Physiology, Ker.C, Islamic Azad University, Kermanshah, Iran Parvin Farzaneghi parvin.farzanegi@gmail.com 10031947532846008122 10031947532846008122 No Department of Exercise Physiology, Sa.C, Islamic Azad University, Sari, Iran