Document Type : Research Paper

Authors

1 Ph.D. Student in Exercise Physiology, Department of Exercise Physiology, Faculty of Literature and Humanies, Shahrekord University, Shahrekord, Iran

2 Associate Professor of Exercise Physiology, Department of Exercise Physiology, Faculty of Literature and Humanies, Shahrekord University, Shahrekord, Iran

3 Associate Professor of Exercise Physiology, Department of Exercise Physiology, Faculty of Literature and Humanies, Shahrekord University, Shahrekord

4 Professor of Clinical Sciences, Department of Veterinary Surgery and Radiology, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran

Abstract

Objective: aging is known as a low bone mass and microarchitectural deterioration of bone tissue, resulting in increased risk of fracture. However, appropriate exercise for the prevention and treatment of osteoporosis has not been determined. The aim of this study was to determine the effects of compare effects of aerobic and resistance exercise training protocols with different intensities on microRNA-133a (mir-133a), Runx2 and Peroxisome proliferator-activated receptors-gamma (PPARγ) in bone marrow Wistar elderly rats. This experimental study was done on 40 Wistar male rats (23-month-old and with an average weight of 441.75 gram). They were randomly divided into five equal groups (n=8) include moderate (60% Maximum voluntary carrying capacity) or high (80% Maximum voluntary carrying capacity) intensity resistance training, moderate (60-110% Maximum speed) or high (80-110% Maximum speed) intensity endurance training and control. The two training groups completed 8 weeks of training program, 5 days a week according to resistance or endurance protocols. After completing training, expression of mir-133a, Runx2 and PPARγ on bone marrow were measured RT-PCR. The statistical analysis was performed using Kruskal-Wallis test with significance level of P

Keywords

Main Subjects

  1. Qi Z, Liu W, Lu J. The mechanisms underlying the beneficial effects of exercise on bone remodeling: Roles of bone-derived cytokines and microRNAs. Prog Biophys Mol. 2016;122(2):131-9.
  2. Rosenthall L, Falutz J, Guaraldi G. The relationships between total body, lumbar spine and femoral neck bone mineral density T-scores for diagnosis of low bone mass in HIV-infected patients. J Clin Nutr Metab. 2018;1:2-5.
  3. Tuck SP, Datta HK. Osteoporosis in the aging male: Treatment options. Clin Interv Aging. 2007;2(4):521-36.
  4. Chen Q, Shou P, Zheng C, Jiang M, Cao G, Yang Q, et al. Fate decision of mesenchymal stem cells: Adipocytes or osteoblasts. Cell Death Differ. 2016;23(7):1128-39.
  5. Delaine-Smith RM, Reilly GC. Mesenchymal stem cell responses to mechanical stimuli. Muscles Ligaments Tendons J. 2012;2(3):169-80.
  6. Fahy N, Alini M, Stoddart MJ. Mechanical stimulation of mesenchymal stem cells: Implications for cartilage tissue engineering. J Orthop Res. 2018;36(1):52-63.
  7. Marędziak M, Śmieszek A, Chrząstek K, Basinska K, Marycz K. Physical activity increases the total number of bone-marrow-derived mesenchymal stem cells, enhances their osteogenic potential, and inhibits their adipogenic properties. Stem Cills Int. 2015;2015: 1-15
  8. Liu SY, Li Z, Xu SY, Xu L, Yang M, Ni GX. Intensity‑dependent effect of treadmill running on differentiation of rat bone marrow stromal cells. Mol Med Rep. 2018;17(6):7746-56.
  9. Hell RCR, Ocarino NM, Boeloni JN, Silva JF, Goes AM, Santos R L. Physical activity improves age‐related decline in the osteogenic potential of rats' bone marrow‐derived mesenchymal stem cells. Acta Physiol. 2012;205(2):292-301.
  10. Franceschi RT, Xiao G. Regulation of the osteoblast‐specific transcription factor, Runx2: Responsiveness to multiple signal transduction pathways. J Cell Biochem. 2003;88(3):446-54.
  11. Zhang Y, Khan D, Delling J, Tobiasch E. Mechanisms underlying the osteo-and adipo-differentiation of human mesenchymal stem cells. Sci World J. 2012;2012:       1-14
  12. Yuan Y, Zhang L, Tong X, Zhang M, Zhao Y, Guo J, et al. Mechanical stress regulates bone metabolism through micrornas. J Cell Physiol. 2017;232(6):1239-45.
  13. Mohan S, Wergedal JE, Das S, Kesavan C. Conditional disruption of miR17-92 cluster in collagen type I-producing osteoblasts results in reduced periosteal bone formation and bone anabolic response to exercise. Phsiyol Genomics. 2014;47(2):   33-43.
  14. Zuo B, Zhu JF, Li J, Wang CD, Zhao XY, Cai GQ, et al. MicroRNA‐103a functions as a mechanosensitive microRNA to inhibit bone formation through targeting runx2. J Bone Miner Res. 2015;30(2):330-45.
  15. Wang H, Sun Z, Wang Y, Hu Z, Zhou H, Zhang L, et al. MiR-33-5p, a novel mechano-sensitive microRNA promotes osteoblast differentiation by targeting Hmga2. Sci Rep-UK. 2016;6:23170-85.
  16. Bailey C, Brooke-Wavell K. Exercise for optimising peak bone mass in women: Postgraduate Symposium. P Nutr Soc. 2008;67(1):9-18.
  17. Kiuchi A, Shimegi S, Tanaka I, Izumo N, Fukuyama R, Nakamuta H, et al. Dose-response effects of exercise intensity on bone in ovariectomized rats. Int J Sport Health Sci. 2006;4:10-8.
  18. Song F, Jiang D, Wang T, Wang Y, Lou Y, Zhang Y. Mechanical stress regulates osteogenesis and adipogenesis of rat mesenchymal stem cells through PI3K/Akt/GSK-3β/β-catenin signaling pathway. Biomed Res Int. 2017; 2017: 6027402-10
  19. Gregov C, Šalaj S. The Effects of Different training modalities on bone mass: a Review. Kinesiol. Int J Fundam Appl Kinesiol. 2014;46(Supplement 1):10-29.
  20. Kohrt WM, Bloomfield SA, Little KD, Nelson ME, Yingling VR. Physical activity and bone health. Med Sci Sports Exerc. 2004;36(11):1985-96.
  21. Turner CH, Robling AG. Mechanisms by which exercise improves bone strength. J Bone Miner Metab. 2005;23(1):16-22.
  22. Markou KB, Mylonas P, Theodoropoulou A, Kontogiannis A, Leglise M, Vagenakis AG, et al. The influence of intensive physical exercise on bone acquisition in adolescent elite female and male artistic gymnasts. J Endocrinol Metab. 2004;89:4383–7.
  23. Maddalozzo GF, Snow CM. High intensity resistance training effects on bone in older men and women. Calcif Tissue Int. 2000;66:399–404.
  24. de Cassia Marqueti R, Almeida JA, Guzzoni V, Boghi F, Renner A, Silva PE, et al. Resistance training minimizes the biomechanical effects of aging in three different rat tendons. J Biomech. 2017;53:29-35.
  25. Krug AL, Macedo AG, Zago AS, Rush JWE, Santos CF, Amaral SL. High-intensity resistance training attenuates dexamethasone-induced muscle atrophy. Muscle Nerve. 2016;53(5):779-88.
  26. Macedo AG, Krug ALO, Herrera NA, Zago AS, Rush JWE, Amaralab SL. Low-intensity resistance training attenuates dexamethasone-induced atrophy in the flexor hallucis longus muscle. J Steroid Biochem Mol Biol. 2014;143:357-64.
  27. Leandro CG, Levada AC, Hirabara SM, Manhães-de-Castro R, De-Castro CB, Curi R, et al. aprogram of moderate physical training for wistar rats based on maximal oxygen consumption. J Strength Cond Res. 2007;21(3):751-6.
  28. Rezaei R, Norshahi M, Bigdeli M, Khodagholi F, Haghparast A. Effect of eight weeks continues and HIIT exercises on VEGF-A and VEGFR-2 levels in stratum, hippocampus and cortex of wistar rat brain. J PHYSIO sport PA. 2016;(16):1213-21. (In Persian).
  29. Fani F, Abbassi Daloii A, Abdi A. The effect of 8 weeks of endurance training and L-NAME on Apelin in adipose tissue in elderly male’s rats. J practi studi bio sport. 2016;4(8):77-88. (In Persian).
  30. Kim SH, Kim GJ, Umemura T, Lee SG, Cho KJ. Aberrant expression of plasma microRNA-33a in an atherosclerosis-risk group. Mol Biol Rep. 2017;44(1):79-88.
  31. Soves CP, Miller JD, Begun DL, Taichman RS, Hankenson KD, Goldsteina SA. Megakaryocytes are mechanically responsive and influence osteoblast proliferation and differentiation. Bone. 2014;66:111-20.
  32. Nie Y, Sato Y, Wang C, Yue F, Kuang S, Gavin TP. impaired exercise tolerance, mitochondrial biogenesis, and muscle fiber maintenance in miR-133a–deficient mice. FASEB Journal. 2016;30(11):3745-58.
  33. Gomes CPC, Oliveira-Jr GP, Madrid B, Almeida JA, Franco OL, Pereira RW. Circulating miR-1, miR-133a, and miR-206 levels are increased after a half-marathon run. Biomarkers. 2014;19(7):585-9.
  34. Nielsen S, Scheele C, Yfanti C, Åkerström T, Nielsen AR, Pedersen BK, et al. Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle. J Physiol. 2010;588(20):4029-37.
  35. Ogasawara R, Akimoto T, Umeno T, Sawada S, Hamaoka T, Fujita S. MicroRNA expression profiling in skeletal muscle reveals different regulatory patterns in high and low responders to resistance training. Physiol Genomics. 2016;48(4):320-4.
  36. Li M, Bai Y, Jianfei C, Xiaodong X, Yuanyuan D, Jing Z. Effects of different exercise intensity on PPARγ and relative index in adolescent obesity rats. Wei Sheng Yan Jiu. 2014;43(5):732-7.
  37. Thomas AW, Davies NA, Moir H, Watkeys L, Ruffino JS, Isa SA, et al. Exercise-associated generation of PPARγ ligands activates PPARγ signaling events and upregulates genes related to lipid metabolism. J Appl Physiol. 2011;112(5): 806-15.
  38. Li Y, Ge C, Long JP, Begun DL, Rodriguez JA, Goldstein SA, et al., Biomechanical stimulation of osteoblast gene expression requires phosphorylation of the RUNX2 transcription factor. J Bone Miner Res. 2012;27(6):1263-74.
  39. Ziros PG Basdra EK, Papavassiliou AG. Runx2: of bone and stretch. Int. J Biochem Cell Biol. 2008;40(9):1659-63.
  40. Singulani MP, Stringhetta-Garcia CT, Santos LF, Morais SRL, Louzada MJQ, Oliveira SHP, et al. Effects of strength training on osteogenic differentiation and bone strength in aging female Wistar rats. Sci Rep-UK. 2017;7(1):42878-9.
  41. Turner CH, Takano Y, Owan I. Aging changes mechanical loading thresholds for bone formation in rats. J Bone Miner Res. 1995;10(10):1544-9.
  42. Aido MIFd. The influence of age and mechanical loading on bone structure and material properties. TU Berlin: IBMS BoneKE; 2015: 84-8
  43. Going SB, Farr JN. Exercise and bone macro-architecture: is childhood a window of opportunity for osteoporosis prevention? Int J Body Compos Res. 2010;8(1):1-9.
  44. Razi H, Birkhold AI, Weinkamer R, Duda GN, Willie BM, Checa S. Aging leads to a dysregulation in mechanically driven bone formation and resorption. J Bone Miner Res. 2015;30(10):1864-73.
  45. Heinonen A, Oja P, Kannus P, Sievanen H, Haapasalo H, Mänttäri A, et al. Bone mineral density in female athletes representing sports with different loading characteristics of the skeleton. Bone. 1995;17(3):197-203.
  46. Wheater G, Elshahaly M, Tuck SP, Datta HK, van Laar JM. The clinical utility of bone marker measurements in osteoporosis. J Transl Med. 2013;11(1):201-14.
  47. Shimamura C, Iwamoto J, Takeda T, Ichimura S, Abe H, Toyama Y. Effect of decreased physical activity on bone mass in exercise-trained young rats. J Orthop Sci. 2002;7(3):358-63.
  48. Sinaki M, Wahner HW, Bergstralh EJ, Hodgson SF, Offord KP, Squires RW, et al. Three-year controlled, randomized trial of the effect of dose-specified loading and strengthening exercises on bone mineral density of spine and femur in nonathletic, physically active women. Bone. 1996;19(3):233-44.
  49. Turner C. Functional determinants of bone structure: beyond Wolff's law of bone transformation. Elsevier. 1992;13(6): 403-9.
  50. Forwood MR, Burr DB. Physical activity and bone mass: Exercises in futility. Bone Miner. 1993;21(2):89-112.
  51. Kotha SP, Hsieh YF, Strigel RM, Muller R, Silva MJ. Experimental and finite element analysis of the rat ulnar loading model-correlations between strain and bone formation following fatigue loading. J Biomech. 2004;37(4):541-8.
  52. Uthgenannt BA, Silva MJ. Use of the rat forelimb compression model to create discrete levels of bone damage in vivo. J Biomech. 2007;40(2):317-24.
  53. Luu YK, Capilla E, Rosen CJ, Gilsanz V, Pessin JE, Judex S, et al. Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary‐induced obesity. J Bone Miner Res. 2009;24(1):50-61.
  54. David V, Martin A, Lafage-Proust MH, Malaval L, Peyroche S, Jones DB, et al. Mechanical loading down-regulates peroxisome proliferator-activated receptor γ in bone marrow stromal cells and favors osteoblastogenesis at the expense of adipogenesis. Endocrinology. 2007;148(5):2553-62.
  55. Sen B, Xie Z, Case N, Ma M, Rubin C, Rubin J. Mechanical strain inhibits adipogenesis in mesenchymal stem cells by stimulating a durable beta-catenin signal. Endocrinology. 2008;149(12):6065-75.
  56. Tanabe Y, Koga M, Saito M, Matsunaga Y, Nakayama K. Inhibition of adipocyte differentiation by mechanical stretching through ERK-mediated downregulation of PPARgamma2. J Cell Sci. 2004;117(16):3605–14
  57. Marie P, Kaabeche K. PPAR gamma activity and control of bone mass in skeletal unloading. Ppar Res. 2006; 2006(1): 1-6.