Top

Published in:

16-05-2024 | Original Article

Treadmill exercise promotes bone tissue recovery in rats subjected to high + Gz loads

Authors: Lilan Gao, Ruiqi Chen, Xianglong Lin, Jie Liu, Jin Liu, Yansong Tan, Chunqiu Zhang, Xizheng Zhang

Published in: Journal of Bone and Mineral Metabolism | Issue 3/2024

Abstract

Introduction

High + Gz loads, the gravitational forces experienced by the body in hypergravity environments, can lead to bone loss in pilots and astronauts, posing significant health risks.

Materials and methods

To explore the effect of treadmill exercise on bone tissue recovery, a study was conducted on 72 male Wistar rats. These rats were subjected to four weeks of varying levels of periodic high + Gz loads (1G, 8G, 20G) experiments, and were subsequently divided into the treadmill group and the control group. The treadmill group underwent a continuous two-week treadmill experiment, while the control group rested during this period. The mechanical properties, microstructure, and molecular markers of their tibial bone tissue were measured using three-point bending, micro-CT, and PCR.

Results

The results showed that treadmill exercise improved the elastic modulus, ultimate deflection, and ultimate load of rat bone tissue. It also increased the number, density, and volume fraction of bone trabeculae, and decreased their separation. Moreover, treadmill exercise enhanced osteogenesis and inhibited osteoclastogenesis.

Conclusion

This study demonstrates that treadmill exercise can promote the recovery of bone tissue in rats subjected to high + Gz loads, providing a potential countermeasure for bone loss in pilots and astronauts.

Lu Y, Shuping W, Biao H, Lilan G, Yang Z, Xizheng Z (2022) Biomedical response of femurs in male wistar rat in chronic hypergravity environments. Medicine in Novel Technology and Devices 16:100161. https://doi.org/10.1016/J.MEDNTD.2022.100161CrossRef

Jamon M, Serradj N (2009) Ground-based researches on the effects of altered gravity on mice development. Microgravity Sci Technol 21:327–337. https://doi.org/10.1007/s12217-008-9098-0CrossRef

Smith SD (1975) Effects of long-term rotation and hypergravity on developing rat femurs. Aviat Space Environ Med 46:248–253 (https://europepmc.org/article/med/1115727)PubMed

Kawashima K, Shibata R, Negishi Y, Endo H (1998) Stimulative effect of high-level hypergravity on differentiated functions of osteoblast-like cells. Cell Struct Funct 23:221–229. https://doi.org/10.1247/csf.23.221CrossRefPubMed

Furutsu M, Kawashima K, Negishi Y, Endo H (2000) Bidirectional effects of hypergravity on the cell growth and differentiated functions of osteoblast-like ROS17/2.8 cells. Biol Pharm Bull 23:1258–1261. https://doi.org/10.1248/bpb.23.1258CrossRefPubMed

Argyrou C, Lambrou GI (2019) Hypergravity and its effects on bones and the musculoskeletal system: a narrative review. Journal of Research and Practice on the Musculoskeletal System 3:1–4. https://doi.org/10.22540/JRPMS-03-001CrossRef

Naumann FL, Bennell KL, Wark JD (2001) The effects of +Gz force on the bone mineral density of fighter pilots. Aviat Space Environ Med 72:177–181 (https://europepmc.org/article/med/11277282)PubMed

Stratos I, Rinas I, Schröpfer K, Hink K, Herlyn P, Bäumler M, Histing T, Bruhn S, Müller-Hilke B, Menger MD, Vollmar B, Mittlmeier T (2023) Effects on bone and muscle upon treadmill interval training in hypogonadal male rats. Biomedicines 11:1370. https://doi.org/10.3390/biomedicines11051370CrossRefPubMedPubMedCentral

Yeh JK, Liu CC, Aloia JF (1993) Effects of exercise and immobilization on bone formation and resorption in young rats. J Appl Physiol Endocrinol Metab 264:E182–E189. https://doi.org/10.1152/ajpendo.1993.264.2.E182CrossRef

10.

Wazzani R, Bourzac C, Elhafci H, Germain P, Ahmaidi S, Pallu S, Jaffré C, Portier H (2023) Comparative effects of various running exercise modalities on femoral bone quality in rats. Eur J Appl Physiol. https://doi.org/10.1007/s00421-023-05293-2CrossRefPubMed

11.

Gao L, Li Y, Yang YJ, Zhang DY (2021) The effect of moderate-intensity treadmill exercise on bone mass and the transcription of peripheral blood mononuclear cells in ovariectomized rats. Front Physiol 12:729910. https://doi.org/10.3389/fphys.2021.729910CrossRefPubMedPubMedCentral

12.

Grasso D, Corsetti R, Lanteri P, Di Bernardo C, Colombini A, Graziani R, Banfi G, Lombardi G (2015) Bone-muscle unit activity, salivary steroid hormones profile, and physical effort over a 3-week stage race. Scand J Med Sci Sports 25:70–80. https://doi.org/10.1111/sms.12147CrossRefPubMed

13.

Gardinier JD, Rostami N, Juliano L, Zhang C (2018) Bone adaptation in response to treadmill exercise in young and adult mice. Bone Rep 8:29–37. https://doi.org/10.1016/j.bonr.2018.01.003CrossRefPubMedPubMedCentral

14.

Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, Turner CH (2008) Mechanical stimulation of bone in vivo reduces osteocyte expression of sost/sclerostin. J Biol Chem 283:5866–5875. https://doi.org/10.1074/jbc.M705092200CrossRefPubMed

15.

Tu X, Rhee Y, Condon KW, Bivi N, Allen MR, Dwyer D, Stolina M, Turner CH, Robling AG, Plotkin LI, Bellido T (2012) Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. Bone 50:209–217. https://doi.org/10.1016/j.bone.2011.10.025CrossRefPubMed

16.

Fang J, Gao J, Gong H, Zhang T, Zhang R, Zhan B (2019) Multiscale experimental study on the effects of different weight-bearing levels during moderate treadmill exercise on bone quality in growing female rats. Biomed Eng Online 18:33. https://doi.org/10.1186/s12938-019-0654-1CrossRefPubMedPubMedCentral

17.

Portier H, Benaitreau D, Pallu S (2020) Does physical exercise always improve bone quality in rats? Life 10:217. https://doi.org/10.3390/life10100217CrossRefPubMedPubMedCentral

18.

Yamamoto T, Ikegame M, Furusawa Y, Tabuchi Y, Hatano K, Watanabe K, Kawago U, Hirayama J, Yano S, Sekiguchi T, Kitamura KI, Endo M, Nagami A, Matsubara H, Maruyama Y, Hattori A, Suzuki N (2022) Osteoclastic and osteoblastic responses to hypergravity and microgravity: analysis using goldfish scales as a bone model. Zoolog Sci 39:388–396. https://doi.org/10.2108/zs210107CrossRef

19.

Lawrence EA, Aggleton J, van Loon J, Godivier J, Harniman R, Pei J, Nowlan N, Hammond C (2021) Exposure to hypergravity during zebrafish development alters cartilage material properties and strain distribution. Bone Joint Res 10:137–148. https://doi.org/10.1302/2046-3758.102.bjr-2020-0239.r1CrossRefPubMedPubMedCentral

20.

Hodkinson PD, Anderton RA, Posselt BN, Fong KJ (2017) An overview of space medicine. Br J Anaesth 119:i143–i153. https://doi.org/10.1093/bja/aex336CrossRefPubMed

21.

Morita S, Nakamura H, Kumei Y, Shimokawa H, Ohya K, Shinomiya K (2004) Hypergravity stimulates osteoblast phenotype expression: a therapeutic hint for disuse bone atrophy. Ann N Y Acad Sci 1030:158–161. https://doi.org/10.1196/annals.1329.020CrossRefPubMed

22.

Bojados M, Herbin M, Jamon M (2013) Kinematics of treadmill locomotion in mice raised in hypergravity. Behav Brain Res 244:48–57. https://doi.org/10.1016/j.bbr.2013.01.017CrossRefPubMed

23.

Iwamoto D, Masaki C, Shibata Y, Watanabe C, Nodai T, Munemasa T, Mukaibo T, Kondo Y, Hosokawa R (2021) Microstructural and mechanical recovery of bone in ovariectomized rats: the effects of menaquinone-7. J Mech Behav Biomed Mater 120:104571. https://doi.org/10.1016/j.jmbbm.2021.104571CrossRefPubMed

24.

Wu Q, Zhong P, Ning P, Tan L, Huang X, Peng T, Yin L, Luo F, Qu M, Zhou J (2022) Treadmill training mitigates bone deterioration via inhibiting NLRP3/Caspase1/IL-1β signaling in aged rats. BMC Musculoskelet Disord 23:1089. https://doi.org/10.1186/s12891-022-06055-5CrossRefPubMedPubMedCentral

25.

Macedo AP, Shimano RC, Ferrari DT, Issa JP, Jordão AA, Shimano AC (2017) Influence of treadmill training on bone structure under osteometabolic alteration in rats subjected to high-fat diet. Scand J Med Sci Sports 27:167–176. https://doi.org/10.1111/sms.12650CrossRefPubMed

26.

Iwamoto J, Shimamura C, Takeda T, Abe H, Ichimura S, Sato Y, Toyama Y (2004) Effects of treadmill exercise on bone mass, bone metabolism, and calciotropic hormones in young growing rats. J Bone Miner Metab 22:26–31. https://doi.org/10.1007/s00774-003-0443-5CrossRefPubMed

27.

Song JQ, Dong F, Li X, Xu CP, Cui Z, Jiang N, Jia JJ, Yu B (2014) Effect of treadmill exercise timing on repair of full-thickness defects of articular cartilage by bone-derived mesenchymal stem cells: an experimental investigation in rats. PLoS ONE 9:e90858. https://doi.org/10.1371/journal.pone.0090858CrossRefPubMedPubMedCentral

28.

Bedford TG, Tipton CM, Wilson NC, Oppliger RA, Gisolfi CV (1979) Maximum oxygen consumption of rats and its changes with various experimental procedures. J Appl Physiol Respir Environ Exerc Physiol 47:1278–1283. https://doi.org/10.1152/jappl.1979.47.6.1278CrossRefPubMed

29.

Canciani B, Ruggiu A, Giuliani A, Panetta D, Marozzi K, Tripodi M, Salvadori PA, Cilli M, Ohira Y, Cancedda R, Tavella S (2015) Effects of long time exposure to simulated micro- and hypergravity on skeletal architecture. J Mech Behav Biomed Mater 51:1–12. https://doi.org/10.1016/j.jmbbm.2015.06.014CrossRefPubMed

30.

Kita S, Iwasaki K, Onishi R, Fujisawa M, Kim H, Shibata S, Ito M (2003) Bone metabolism and formation of mice bred in a 2 G environment. Adv Space Res 32:1453–1457. https://doi.org/10.1016/s0273-1177(03)90380-2CrossRefPubMed

31.

Vico L, Barou O, Laroche N, Alexandre C, Lafage-Proust MH (1999) Effects of centrifuging at 2g on rat long bone metaphyses. Eur J Appl Physiol 80:360–366. https://doi.org/10.1007/s004210050604CrossRef

32.

Martinez DA, Orth MW, Carr KE, Vanderby R Jr, Vasques M, Grindeland RE, Vailas AC (1998) Cortical bone responses to 2G hypergravity in growing rats. Aviat Space Environ Med 69:17–22 (https://www.researchgate.net/publication/12541185_Cortical_bone_responses_to_2G_hypergravity_in_growing_rats)

33.

Kohles SS, Bowers JR, Vailas AC, Vanderby R Jr (1996) Effect of a hypergravity environment on cortical bone elasticity in rats. Calcif Tissue Int 59:214–217. https://doi.org/10.1007/s002239900111CrossRefPubMed

34.

Kawao N, Morita H, Obata K, Tamura Y, Okumoto K, Kaji H (2016) The vestibular system is critical for the changes in muscle and bone induced by hypergravity in mice. Physiol Rep 4:e12979. https://doi.org/10.14814/phy2.12979CrossRefPubMedPubMedCentral

35.

Guéguinou N, Bojados M, Jamon M, Derradji H, Baatout S, Tschirhart E, Frippiat JP, Legrand-Frossi C (2012) Stress response and humoral immune system alterations related to chronic hypergravity in mice. Psychoneuroendocrinology 37:137–147. https://doi.org/10.1016/j.psyneuen.2011.05.015CrossRefPubMed

36.

Ikawa T, Kawaguchi A, Okabe T, Ninomiya T, Nakamichi Y, Nakam M, Uehara S, Nakamura H, Udagawa N, Takahashi N, Nakam H, Wakitani S (2011) Hypergravity suppresses bone resorption in ovariectomized rats. Adv Space Res 47:1214–1224. https://doi.org/10.1016/j.asr.2010.12.004CrossRef

37.

Gnyubkin V, Guignandon A, Laroche N, Vanden-Bossche A, Normand M, Lafage-Proust MH, Vico L (2015) Effects of chronic hypergravity: from adaptive to deleterious responses in growing mouse skeleton. J Appl Physiol 119:908–917. https://doi.org/10.1152/japplphysiol.00364.2015CrossRefPubMed

38.

Yasuda H (2021) Discovery of the RANKL/RANK/OPG system. J Bone Miner Metab 39:2–11. https://doi.org/10.1007/s00774-020-01175-1CrossRefPubMed

39.

Li CW, Liang B, Shi XL, Wang H (2015) Opg/Rankl mRNA dynamic expression in the bone tissue of ovariectomized rats with osteoporosis. Genet Mol Res 14:9215–9224. https://doi.org/10.4238/2015.August.10.1CrossRefPubMed

40.

Cusick JF, Yoganandan N (2002) Biomechanics of the cervical spine 4: major injuries. Clin Biomech (Bristol, Avon) 17:1–20. https://doi.org/10.1016/s0268-0033(01)00101-2CrossRefPubMed

41.

Cowin SC (1986) Wolff’s law of trabecular architecture at remodeling equilibrium. J Biomech Eng 108:83–88. https://doi.org/10.1115/1.3138584CrossRefPubMed

42.

Frost HM (1990) Skeletal structural adaptations to mechanical usage (SATMU): 3. the hyaline cartilage modeling problem. Anat Rec 226:423–432. https://doi.org/10.1002/ar.1092260404CrossRefPubMed

43.

Frost HM (1990) Skeletal structural adaptations to mechanical usage (SATMU): 2. redefining Wolff’s law: the remodeling problem. Anat Rec 226:414–422. https://doi.org/10.1002/ar.1092260403CrossRefPubMed

44.

Frost HM (1990) Skeletal structural adaptations to mechanical usage (SATMU): 1. redefining wolff’s law: the bone modeling problem. Anat Rec 226:403–413. https://doi.org/10.1002/ar.1092260402CrossRefPubMed

45.

Tang L, Guo H, Wang K, Zhou Y, Wu T, Fan X, Guo J, Sun L, Ta D (2023) Low-intensity pulsed ultrasound enhances the positive effects of high-intensity treadmill exercise on bone in rats. J Bone Miner Metab 41:592–605. https://doi.org/10.1007/s00774-023-01439-6CrossRefPubMed

46.

Friedman MA, Kohn DH (2022) Calcium and phosphorus supplemented diet increases bone volume after thirty days of high speed treadmill exercise in adult mice. Sci Rep 12:14616. https://doi.org/10.1038/s41598-022-19016-8CrossRefPubMedPubMedCentral

47.

Huiskes R, Ruimerman R, van Lenthe GH, Janssen JD (2000) Effects of mechanical forces on maintenance and adaptation of form in trabecular bone. Nature 405:704–706. https://doi.org/10.1038/35015116CrossRefPubMed

48.

Moreira LD, Oliveira ML, Lirani-Galvão AP, Marin-Mio RV, Santos RN, Lazaretti-Castro M (2014) Physical exercise and osteoporosis: effects of different types of exercises on bone and physical function of postmenopausal women. Arq Bras Endocrinol Metabol 58:514–522. https://doi.org/10.1590/0004-2730000003374CrossRefPubMed

49.

Hagihara Y, Fukuda S, Goto S, Iida H, Yamazaki M, Moriya H (2005) How many days per week should rats undergo running exercise to increase BMD? J Bone Miner Metab 23:289–294. https://doi.org/10.1007/s00774-005-0601-zCrossRefPubMed

50.

Roghani T, Torkaman G, Movasseghe S, Hedayati M, Goosheh B, Bayat N (2013) Effects of short-term aerobic exercise with and without external loading on bone metabolism and balance in postmenopausal women with osteoporosis. Rheumatol Int 33:291–298. https://doi.org/10.1007/s00296-012-2388-2CrossRefPubMed

51.

Le Pense S, Chen Y (2017) Contribution of fluid in bone extravascular matrix to strain-rate dependent stiffening of bone tissue – a poroelastic study. J Mech Behav Biomed Mater 65:90–101. https://doi.org/10.1016/j.jmbbm.2016.08.016CrossRefPubMed

52.

Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R (2010) Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res 25:1468–1486. https://doi.org/10.1002/jbmr.141CrossRefPubMed

53.

Prisby RD (2017) Mechanical, hormonal and metabolic influences on blood vessels, blood flow and bone. J Endocrinol 235:R77-r100. https://doi.org/10.1530/joe-16-0666CrossRefPubMedPubMedCentral

54.

Cheung WH, Sun MH, Zheng YP, Chu WC, Leung AH, Qin L, Wei FY, Leung KS (2012) Stimulated angiogenesis for fracture healing augmented by low-magnitude, high-frequency vibration in a rat model-evaluation of pulsed-wave doppler, 3-D power doppler ultrasonography and micro-CT microangiography. Ultrasound Med Biol 38:2120–2129. https://doi.org/10.1016/j.ultrasmedbio.2012.07.025CrossRefPubMed

55.

Barou O, Mekraldi S, Vico L, Boivin G, Alexandre C, Lafage-Proust MH (2002) Relationships between trabecular bone remodeling and bone vascularization: a quantitative study. Bone 30:604–612. https://doi.org/10.1016/s8756-3282(02)00677-4CrossRefPubMed

Title: Treadmill exercise promotes bone tissue recovery in rats subjected to high + Gz loads
Authors: Lilan Gao
Ruiqi Chen
Xianglong Lin
Jie Liu
Jin Liu
Yansong Tan
Chunqiu Zhang
Xizheng Zhang
Publication date: 16-05-2024
Publisher: Springer Nature Singapore
Published in: Journal of Bone and Mineral Metabolism / Issue 3/2024
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-024-01513-7

PD Dr. Carsten W. Israel

Developed by: Springer Medizin

Start the cases

At a glance: The STEP trials

Obesity Clinical Trial Summary

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

2024 ESC Congress

Springer Medicine

Treadmill exercise promotes bone tissue recovery in rats subjected to high + Gz loads

Abstract

Introduction

Materials and methods

Results

Conclusion

2024 ESC Congress

Noise pollution dangerous for heart health

Post-TAVI follow up: deploying virtual assistants

Antihypertensives: more effective at morning or night?

Low Lp(a) levels unlikely to increase the risk of diabetes

» View more highlights on the 2024 ESC Congress hub page

A quick guide to ECGs

At a glance: The STEP trials

2024 ESC Congress

Springer Medicine

Abstract

Introduction

Materials and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2024

Effect of plate orientation on apparent thickness of mineral plates by transmission electron microscopy

Prevalence of osteosarcopenia and its association with mortality and fractures among patients undergoing hemodialysis

Achieving osteoporosis treat-to-target goals with teriparatide or alendronate: sub-analysis of Japanese Osteoporosis Intervention Trial-05 (JOINT-05)

Effectiveness of calcimimetics on fractures in dialysis patients with secondary hyperparathyroidism: meta-analysis of randomized trials

Falls, fracture and frailty risk in multiple sclerosis: a Mendelian Randomization study to identify shared genetics

Sex-specific association of serum dehydroepiandrosterone and its sulfate levels with osteoporosis in type 2 diabetes

2024 ESC Congress

Noise pollution dangerous for heart health

Post-TAVI follow up: deploying virtual assistants

Antihypertensives: more effective at morning or night?

Low Lp(a) levels unlikely to increase the risk of diabetes

» View more highlights on the 2024 ESC Congress hub page

A quick guide to ECGs

At a glance: The STEP trials