Skip to main content
Log in

Can balneotherapy modify microRNA expression levels in osteoarthritis? A comparative study in patients with knee osteoarthritis

  • Original Paper
  • Published:
International Journal of Biometeorology Aims and scope Submit manuscript

Abstract

The aim of this study was to evaluate the whole-blood levels of miR-155, miR-223, miR-181a, miR-146a, and miR-let-7e in patients with bilateral knee osteoarthritis (OA) after a cycle of mud-bath therapy (MBT). Thirty-two patients with knee OA defined by the ACR criteria were included. Twenty-one patients (MBT group) were daily treated with a combination of local mud-packs at 42 °C and baths in mineral water, at 37 °C for 15 min, for 12 applications over a period of 2 weeks, in addition to standard therapy; 11 patients (control group) continued their conventional treatment alone. Global pain score evaluated by visual analog scale (VAS), WOMAC subscores, and microRNA expression were evaluated at baseline and after 2 weeks. Peripheral whole blood was collected into PAXgene™ Blood RNA tubes, stored at − 80 °C, and total RNA was extracted. The expression of miR-155, miR-223, miR-181a, miR-146a, and miR-let-7e was determined by qRT-PCR. After MBT, we observed a statistically significant improvement of clinical parameters and a significant decrease of miR-155, miR-181a, miR-146a (p < 0.001), and miR-223 (p < 0.01) expression levels. No clinical and biochemical modifications were detected in the control group. No significant variations of miR-let-7e were shown in both groups after 2 weeks. In conclusion, MBT can modify the expression of miR-155, miR-181a, miR-146a, and miR-223, which are upregulated in OA. It could be due to the heat stress and the hydrostatic pressure, since some miRNAs were found to be temperature- and mechano-responsive. Further studies are needed to better explain the mechanism of action of MBT and the role of miRNAs in OA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Altman R, Asch E, Bloch D et al (1986) Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 29:1039–1049

    Article  CAS  Google Scholar 

  • Aziz F (2016) The emerging role of miR-223 as novel potential diagnostic and therapeutic target for inflammatory disorders. Cell Immunol 303:1–6. doi:10.1016/j.cellimm.2016.04.003

    Article  CAS  Google Scholar 

  • Bellamy N, Buchanan WW, Goldsmith CH et al (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833–1840

    CAS  Google Scholar 

  • Bender T, Karagülle Z, Bálint GP et al (2005) Hydrotherapy, balneotherapy, and spa treatment in pain management. Rheumatol Int 25:220–224

    Article  Google Scholar 

  • Beyer C, Zampetaki A, Lin NY et al (2015) Signature of circulating microRNAs in osteoarthritis. Ann Rheum Dis 74:e18. doi:10.1136/annrheumdis-2013-204698

    Article  Google Scholar 

  • Cheleschi S, De Palma A, Pecorelli A et al (2017) Hydrostatic pressure regulates microRNA expression levels in osteoarthritic chondrocyte cultures via the Wnt/β-catenin pathway. Int J Mol Sci 18:E133. doi:10.3390/ijms18010133

    Article  Google Scholar 

  • Ciani O, Pascarelli NA, Giannitti C et al (2016) Mud-bath therapy in addition to usual care in bilateral knee osteoarthritis: economic evaluation alongside a randomized controlled trial. Arthritis Care Res (Hoboken). doi:10.1002/acr.23116

  • De Palma A, Cheleschi S, Pascarelli NA et al (2017) Do MicroRNAs have a key epigenetic role in osteoarthritis and in mechanotransduction? Clin Exp Rheumatol 35:518

    Google Scholar 

  • Díaz-Prado S, Cicione C, Muiños-López E et al (2012) Characterization of microRNA expression profiles in normal and osteoarthritic human chondrocytes. BMC Musculoskelet Disord 13:144. doi:10.1186/1471-2474-13-144

    Article  Google Scholar 

  • Fioravanti A, Cantarini L, Guidelli GM et al (2011) Mechanisms of action of spa therapies in rheumatic diseases: what scientific evidence is there? Rheumatol Int 31:1–8. doi:10.1007/s00296-010-1628-6

    Article  Google Scholar 

  • Fioravanti A, Bacaro G, Giannitti C et al (2015) One-year follow-up of mud-bath therapy in patients with bilateral knee osteoarthritis: a randomized, single-blind controlled trial. Int J Biometeorol 59:1333–1343. doi:10.1007/s00484-014-0943-0

    Article  CAS  Google Scholar 

  • Guan YJ, Yang X, Wei L et al (2011) MiR-365: a mechanosensitive microRNA stimulates chondrocyte differentiation through targeting histone deacetylase 4. FASEB J 25:4457–4466. doi:10.1096/fj.11-185132

    Article  CAS  Google Scholar 

  • Hochberg MC, Altman RD, April KT et al (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

    Article  CAS  Google Scholar 

  • Marques-Rocha JL, Samblas M, Milagro FI et al (2015) Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB J 29:3595–3611. doi:10.1096/fj.14-260323

    Article  CAS  Google Scholar 

  • McAlindon TE, Bannuru RR, Sullivan MC et al (2014) OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil 22:363–388. doi:10.1016/j.joca.2014.01.003

    Article  CAS  Google Scholar 

  • Murata K, Yoshitomi H, Tanida S et al (2010) Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis Res Ther 12:R86. doi:10.1186/ar3013

    Article  Google Scholar 

  • Nakamura A, Rampersaud YR, Sharma A et al (2016) Identification of microRNA-181a-5p and microRNA-4454 as mediators of facet cartilage degeneration. JCI Insight 1(12):e86820

    Article  Google Scholar 

  • Okuhara A, Nakasa T, Shibuya H et al (2012) Changes in microRNA expression in peripheral mononuclear cells according to the progression of osteoarthritis. Mod Rheumatol 22:446–457. doi:10.1007/s10165-011-0536-2

    Article  CAS  Google Scholar 

  • Potla R, Singh IS, Atamas SP et al (2015) Shifts in temperature within the physiologic range modify strand-specific expression of select human microRNAs. RNA 21:1261–1273. doi:10.1261/rna.049122.114

    Article  CAS  Google Scholar 

  • Rainen L, Oelmueller U, Jurgensen S et al (2002) Stabilization of mRNA expression in whole-blood samples. Clin Chem 48:1883–1890

    CAS  Google Scholar 

  • Ramakers C, Ruijter JM, Deprez RH et al (2003) Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett 339:62–66

    Article  CAS  Google Scholar 

  • Salaffi F, Leardini G, Canesi B et al (2003) Reliability and validity of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index in Italian patients with osteoarthritis of the knee. Osteoarthr Cartil 11:551–560

    Article  CAS  Google Scholar 

  • Tenti S, Cheleschi S, Galeazzi M et al (2015) Spa therapy: can be a valid option for treating knee osteoarthritis? Int J Biometeorol 59:1133–1143. doi:10.1007/s00484-014-0913-6

    Article  Google Scholar 

  • Vandesompele J, De Preter K, Pattyn F et al (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3:1–12

    Article  Google Scholar 

  • Wilmink GJ, Roth CL, Ibey BL et al (2010) Identification of microRNAs associated with hyperthermia-induced cellular stress response. Cell Stress Chaperones 15:1027–1038. doi:10.1007/s12192-010-0189-7

    Article  CAS  Google Scholar 

  • Yuan Y, Zhang L, Tong X et al (2017) Mechanical stress regulates bone metabolism through microRNAs. J Cell Physiol 232:1239–1245. doi:10.1002/jcp.2568

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors affirm that there are no undeclared contributors, funding sources or study sponsors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonella Fioravanti.

Ethics declarations

The study was performed according to the Declaration of Helsinki; it was approved by the medical ethics committee (Siena University Hospital, decision no. 340, August 12, 2010) and was registered on http://www.clinicaltrials.gov (NCT01538043).

Competing interests

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Giannitti, C., De Palma, A., Pascarelli, N.A. et al. Can balneotherapy modify microRNA expression levels in osteoarthritis? A comparative study in patients with knee osteoarthritis. Int J Biometeorol 61, 2153–2158 (2017). https://doi.org/10.1007/s00484-017-1420-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00484-017-1420-3

Keywords

Navigation