Abstract
Introduction
To investigate the effect of different frequencies of whole body vibration (WBV) on articular cartilage of early knee osteoarthritis (OA) rats and determine whether WBV would influence the pathway of hypoxia-inducible factor-2α (HIF-2α) regulation-related genes after 8 weeks of treatment.
Materials and methods
Forty 8-week-old OA rats were divided into five groups: sham control (SC); high frequency 60 Hz (HV1); high frequency 40 Hz (HV2); middle frequency 20 Hz (MV) and low frequency 10 Hz (LV). WBV (0.3 g) treatment was given 40 min/day and 5 days/week. After 8 weeks, rats were killed and knees were harvested. OA grading score: Osteoarthritis Research Society International (OARSI), and the expression of related genes: interleukin-1β (IL-1β), HIF-2α, matrix metalloproteinases-13 (MMP-13), and collagen type II alpha 1 (COL2A1), at both mRNA and protein levels were analyzed.
Results
After 8 weeks of WBV, our data showed that lower frequency (10 Hz) was more effective than the higher ones, yet they all suggested that WBV alleviates the erosion of knee articular cartilage in early OA. The expression of IL-1β, HIF-2α and MMP-13 decreased with frequency and reached the lowest level at 10 Hz, the expression of COL2A1 increased with frequency and reached the highest level at 10 Hz.
Conclusions
This study demonstrates that WBV could alleviate the degeneration of knee joints in an early OA rat model. WBV regulates related gene expression at both mRNA and protein levels. HIF-2α could be a therapeutic target. The effect of WBV is frequency dependent; the lower frequency shows better effects.
Similar content being viewed by others
References
Befrui N, Elsner J, Flesser A, Huvanandana J, Jarrousse O, Le TN, Muller M, Schulze WHW, Taing S, Weidert S (2018) Vibroarthrography for early detection of knee osteoarthritis using normalized frequency features. Med Biol Eng Comput 56:1499–1514
Xiao ZF, Su GY, Hou Y, Chen SD, Lin DK (2018) Cartilage degradation in osteoarthritis: A process of osteochondral remodeling resembles the endochondral ossification in growth plate? Med Hypotheses 121:183–187
Neogi T (2013) The epidemiology and impact of pain in osteoarthritis. Osteoarthr Cartil 21:1145–1153
Guilak F, Nims RJ, Dicks A, Wu CL, Meulenbelt I (2018) Osteoarthritis as a disease of the cartilage pericellular matrix. Matrix Biol 71–72:40–50
Xu X, Li X, Liang Y, Ou Y, Huang J, Xiong J, Duan L, Wang D (2019) Estrogen modulates cartilage and subchondral bone remodeling in an ovariectomized rat model of postmenopausal osteoarthritis. Med Sci Monit 25:3146–3153
Mobasheri A, Bay-Jensen AC, van Spil WE, Larkin J, Levesque MC (2017) Osteoarthritis year in review 2016: biomarkers (biochemical markers). Osteoarthr Cartil 25:199–208
Watt FE (2018) Osteoarthritis biomarkers: year in review. Osteoarthr Cartil 26:312–318
Hochberg M, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, Towheed T, Welch V, Wells G, Tugwell P (2012) American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken) 64:465–474
del Pozo-Cruz B, Adsuar JC, Parraca JA, del Pozo-Cruz J, Olivares PR, Gusi N (2012) Using whole-body vibration training in patients affected with common neurological diseases: a systematic literature review. J Altern Complement Med 18:29–41
Lai Z, Wang X, Lee S, Hou X, Wang L (2017) Effects of whole body vibration exercise on neuromuscular function for individuals with knee osteoarthritis: study protocol for a randomized controlled trial. Trials 18:437
Salmon JR, Roper JA, Tillman MD (2012) Does acute whole-body vibration training improve the physical performance of people with knee osteoarthritis? J Strength Cond Res 26:2983–2989
Rogan S, de Bruin ED, Radlinger L, Joehr C, Wyss C, Stuck NJ, Bruelhart Y, de Bie RA, Rs H (2015) Effects of whole-body vibration on proxies of muscle strength in old adults: a systematic review and meta-analysis on the role of physical capacity level. Eur Rev Aging Phys Act 12:12
Rogan S, Rs H (2012) Trainingsmethoden-Muskelkraftsteigerung durch Ganzkörpervibration – Kraft mit Hertz. Sportverletz Sportschaden 26:185–187
Ferreira RM, Duarte JA, Gonçalves RS (2018) Non-pharmacological and non-surgical interventions to manage patients with knee osteoarthritis: an umbrella review. Acta Reumatol Port 43:182–200
Rauch F (2009) Vibration therapy. Dev Med Child Neuro 51:166–168
Tsuji T, Yoon J, Aiba T, Kanamori A, Okura T, Tanaka K (2014) Effects of whole-body vibration exercise on muscular strength and power, functional mobility and self-reported knee function in middle-aged and older Japanese women with knee pain. Knee 21:1088–1095
Wang P, Yang L, Liu C, Wei X, Yang X, Zhou Y, Jiang H, Lei Z, Reinhardt JD, He C (2016) Effects of whole body vibration exercise associated with quadriceps resistance exercise on functioning and quality of life in patients with knee osteoarthritis: a randomized controlled trial. Clin Rehabil 30:1074–1087
Lorenz H, Wenz W, Ivancic M, Steck E, Ws R (2005) Early and stable upregulation of collagen type II, collagen type I and YKL40 expression levels in cartilage during early experimental osteoarthritis occurs independent of joint location and histological grading. Arthritis Res Ther 7:R156–R165
Sutter EG, Widmyer MR, Utturkar GM, Spritzer CE, Garrett WE, DeFrate LE (2015) In vivo measurement of localized tibiofemoral cartilage strains in response to dynamic activity. Am J Sports Med 43:370–376
Wang CT, Lin YT, Chiang BL, Lin YH, Hou SM (2006) High molecular weight hyaluronic acid down-regulates the gene expression of osteoarthritis-associated cytokines and enzymes in fibroblast-like synoviocytes from patients with early osteoarthritis. Osteoarthritis Cartil 14:1237–1247
Charlier E, Relic B, Deroyer C, Malaise O, Neuville S, Collée J, Malaise MG, De Seny DS (2016) Insights on molecular mechanisms of chondrocytes death in osteoarthritis. Int J Mol Sci 17:2146
Speichert S, Molotkov N, El Bagdadi K, Meurer A, Zaucke F, Jenei-Lanzl Z (2019) Role of norepinephrine in IL-1beta-induced chondrocyte dedifferentiation under physioxia. Int J Mol Sci 20:1212
Yang S, Kim J, Ryu JH, Oh H, Chun CH, Kim BJ, Min BH, Chun JS (2010) Hypoxia-inducible factor-2alpha is a catabolic regulator of osteoarthritic cartilage destruction. Nat Med 16:687–693
Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S, Nishida N, Akune T, Yoshimura N, Nakagawa T, Nakamura K, Tokunaga K, Chung UI, Kawaguchi H (2010) Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med 16:678–686
Little CB, Barai A, Burkhardt D, Smith SM, Fosang AJ, Werb Z, Shah M, Thompson EW (2009) Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum 60:3723–3733
Wang YJ, Shen M, Wang S, Wen X, Han XR, Zhang ZF, Li H, Wang F, Wu DM, Lu J, Zheng YL (2017) Inhibition of the TGF-β1/Smad signaling pathway protects against cartilage injury and osteoarthritis in a rat model. Life Sci 189:106–113
Junbo W, Sijia L, Hongying C, Lei L, Pu W (2017) Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis. BMC Musculoskelet Disord 18:260
Templin JS, Wylie MC, Kim JD, Kurgansky KE, Gorski G, Kheir J, Zurakowski D, Corfas G, Berde C (2015) Neosaxitoxin in rat sciatic block: improved therapeutic index using combinations with bupivacaine, with and without epinephrine. Anesthesiology 123:886–898
Li A, Zhang Y, Lao L, Xin J, Ren K, Berman BM, Zhang RX (2011) Serotonin receptor 2A/c is involved in electroacupuncture inhibition of pain in an osteoarthritis rat model. Evid Based Complement Alternat Med 2011:619650
Yang Y, Wang Y, Kong Y, Zhang X, Bai L (2017) The effects of different frequency treadmill exercise on lipoxin A4 and articular cartilage degeneration in an experimental model of monosodium iodoacetate-induced osteoarthritis in rats. PLoS ONE 12:e0179162
Pritzker KPH, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, Salter D, van den Berg WB (2006) Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartil 14:13–29
Qin J, Chow SK, Guo A, Wong WN, Leung KS, Cheung WH (2014) Low magnitude high frequency vibration accelerated cartilage degeneration but improved epiphyseal bone formation in anterior cruciate ligament transect induced osteoarthritis rat model. Osteoarthritis Cartil 22:1061–1067
McCann MR, Yeung C, Pest MA, Ratneswaran A, Pollmann SI, Holdsworth DW, Beier F, Dixon SJ, Seguin CA (2017) Whole-body vibration of mice induces articular cartilage degeneration with minimal changes in subchondral bone. Osteoarthritis Cartil 25:770–778
Kerr GJ, McCann MR, Branch JK, Ratneswaran A, Pest MA, Holdsworth DW, Beier F, Dixon SJ, Seguin CA (2017) C57BL/6 mice are resistant to joint degeneration induced by whole-body vibration. Osteoarthritis Cartil 25:421–425
Ishizuka S, Sakai T, Hiraiwa H, Hamada T, Knudson W, Omachi T, Ono Y, Nakashima M, Matsukawa T, Oda T, Takamatsu A, Yamashita S, Ishiguro N (2016) Hypoxia-inducible factor-2alpha induces expression of type X collagen and matrix metalloproteinases 13 in osteoarthritic meniscal cells. Inflamm Res 65:439–448
Pickarski M, Hayami T, Zhuo Y, Duong LT (2011) Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. BMC Musculoskelet Disord 12:2–14
McCann MR, Patel P, Pest MA, Ratneswaran A, Lalli G, Beaucage KL, Backler GB, Kamphuis MP, Esmail Z, Lee J, Barbalinardo M, Mort JS, Holdsworth DW, Beier F, Dixon SJ, Seguin CA (2015) Repeated exposure to high-frequency low-amplitude vibration induces degeneration of murine intervertebral discs and knee joints. Arthritis Rheumatol 67:2164–2175
Tankisheva E, Jonkers I, Boonen S, Delecluse C, van Lenthe GH, Druyts HL, Spaepen P, Verschueren SM (2013) Transmission of whole-body vibration and its effect on muscle activation. J Strength Cond Res 27:2533–2541
Kim JE, Song DH, Kim SH, Jung Y, Kim SJ (2018) Development and characterization of various osteoarthritis models for tissue engineering. PLoS ONE 13:e0194288
Zafar H, Alghadir A, Anwer S, Al-Eisa E (2015) Therapeutic effects of whole-body vibration training in knee osteoarthritis: a systematic review and meta-analysis. Arch Phys Med Rehabil 96:1525–1532
McCann MR, Veras MA, Yeung C, Lalli G, Patel P, Leitch KM, Holdsworth DW, Dixon SJ, Séguin CA (2017) Whole-body vibration of mice induces progressive degeneration of intervertebral discs associated with increased expression of Il-1β and multiple matrix degrading enzymes. Osteoarthritis Cartil 25:779–789
Bernardo-Filho M, Bemben D, Stark C, Taiar R (2018) Biological consequences of exposure to mechanical vibration. Dose Response 16:1559325818799618
Giombini A, Menotti F, Laudani L, Piccinini A, Fagnani F, Di Cagno A, Macaluso A, Pigozzi F (2015) Effect of whole body vibration frequency on neuromuscular activity in ACL-deficient and healthy males. Biol Sport 32:243–247
Zhang S, An Q, Hu P, Wu X, Pan X, Peng W, Wang R, Gan J, Chen D, Li Z, Wang T, Zhou G (2019) Core regulatory RNA molecules identified in articular cartilage stem/progenitor cells during osteoarthritis progression. Epigenomics 11:669–684
Tang J, Su N, Zhou S, Xie Y, Huang J, Wen X, Wang Z, Wang Q, Xu W, Du X, Chen H, Ls C (2016) Fibroblast growth factor receptor 3 inhibits osteoarthritis progression in the knee joints of adult mice. Arthritis Rheumatol 68:2432–2443
Pamon T, Bhandal V, Adler BJ, Ete Chan M, Rubin CT (2018) Low-intensity vibration increases cartilage thickness in obese mice. J Orthop Res 36:751–759
Buckley MR, Bonassar LJ, Cohen I (2013) Localization of viscous behavior and shear energy dissipation in articular cartilage under dynamic shear loading. J Biomech Eng 135:31002
Poulet B (2016) Non-invasive Loading Model of Murine Osteoarthritis. Curr Rheumatol Rep 18:40
Kim JR, Yoo JJ, Kim HA (2018) Therapeutics in osteoarthritis based on an understanding of its molecular pathogenesis. Int J Mol Sci 19:674
Acknowledgements
This research was supported in part by Anhui Natural Science Foundation (China) under Award Number 1508085MH181. The content of the work is solely the responsibility of the authors and does not necessarily represent the official views of the funders. The funders had no role in the design, data collection, analysis, and interpretation of data, in the writing of the manuscript or in the decision to submit the manuscript for publication. Funding sources are not associated with the scientific contents of the study. We gratefully acknowledge the cooperation of other participants who took time out of their schedules to help with this project.
Author information
Authors and Affiliations
Contributions
ZBW oversaw the project; LW and ZBW designed the study; LW and QQL conducted the experiments; JCS and TMW analyzed and interpreted data; LW and TL participated in drafting the main manuscript text; ZBW and TMW revised the article critically. All authors contributed to writing or reviewing the manuscript and final approval.
Corresponding author
Ethics declarations
Conflict of interest
All authors have no conflicts of interest.
Ethical approval
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This research was approved by the Ethics Committee of Animal Experiments of Anhui University of Chinese Medicine.
Informed consent
This study does not involve human participants and, therefore, does not require informed consent.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Wang, L., Wang, Z., Liu, Q. et al. Effect of whole body vibration on HIF-2α expression in SD rats with early knee osteoarthritis. J Bone Miner Metab 38, 491–500 (2020). https://doi.org/10.1007/s00774-020-01092-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00774-020-01092-3