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A preliminary analysis of microRNA profiles in the subchondral bone between Kashin-Beck disease and primary knee osteoarthritis

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Abstract

Introduction

Kashin-Beck disease (KBD) is a chronic osteochondral disorder primarily associated with cartilage degeneration. The bone texture structure in KBD was also changed but it was not identical to primary knee osteoarthritis (OA). This study investigates the differences in microRNA (miRNA) profiles of subchondral bone collected from patients suffering from KBD in comparison with those with primary knee osteoarthritis (OA).

Methods

Subchondral bone tissues were taken from four patients with KBD and four patients with primary knee OA undergoing total knee replacement. The miRNA array profiling was performed using an Affymetrix miRNA 4.0 Array, and then the target gene predictions and function annotations of the predicted targets were performed.

Results

Our results showed that 124 miRNAs had lower expression levels in the subchondral bone sampled from KBD patients in comparison with OA patients. Gene ontology (GO) and KEGG pathway analyses of the predicted targets demonstrated numerous significantly enriched GO terms and signal pathways essential for bone development and integrity, such as metabolic processes, PI3K-Akt, and MAPK signaling pathways.

Conclusions

Our study confirms that a large set of miRNAs are differentially expressed in the subchondral bone of patients with KBD and OA and contributes new insights into potential pathological changes in the subchondral bone of KBD patients.

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References

  1. Hinsenkamp M (2001) Kashin-Beck disease. Int Orthop 25(3):133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Guo X, Ma WJ, Zhang F, Ren FL, Qu CJ, Lammi MJ (2014) Recent advances in the research of an endemic osteochondropathy in China: Kashin-Beck disease. Osteoarthr Cartil 22(11):1774–1783. https://doi.org/10.1016/j.joca.2014.07.023

    Article  CAS  Google Scholar 

  3. Yang L, Zhao GH, Liu H, Wang X, Guo X, Lammi MJ (2016) Field synopsis and meta-analyses of genetic epidemiological evidence for Kashin-Beck disease, an endemic osteoarthropathy in China. Mol Gen Genomics 291(5):1823–1833. https://doi.org/10.1007/s00438-016-1222-z

    Article  CAS  Google Scholar 

  4. Pasteels JL, Liu FD, Hinsenkamp M, Rooze M, Mathieu F, Perlmutter N (2001) Histology of Kashin-Beck lesions. Int Orthop 25(3):151–153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Martel-Pelletier J, Barr AJ, Cicuttini FM, Conaghan PG, Cooper C, Goldring MB, Goldring SR, Jones G, Teichtahl AJ, Pelletier JP (2016) Osteoarthritis. Nat Rev Dis Primers 2:16072. https://doi.org/10.1038/nrdp.2016.72

    Article  PubMed  Google Scholar 

  6. Guo X (2001) Diagnostic, clinical and radiological characteristics of Kashin-Beck disease in Shaanxi Province, PR China. Int Orthop 25(3):147–150

    Article  Google Scholar 

  7. Mathieu F, Begaux F, Lan ZY, Suetens C, Hinsenkamp M (1997) Clinical manifestations of Kashin-Beck disease in Nyemo Valley, Tibet. Int Orthop 21(3):151–156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Li Y, Zhou Z, Shen B, Yang J, Kang P, Yang X, Liu G, Pei F (2013) Clinical features of Kashin-Beck disease in adults younger than 50 years of age during a low incidence period: severe elbow and knee lesions. Clin Rheumatol 32(3):317–324. https://doi.org/10.1007/s10067-012-2115-0

    Article  PubMed  Google Scholar 

  9. Schepman K, Engelbert RH, Visser MM, Yu C, de Vos R (2011) Kashin Beck disease: more than just osteoarthrosis: a cross-sectional study regarding the influence of body function-structures and activities on level of participation. Int Orthop 35(5):767–776. https://doi.org/10.1007/s00264-010-1043-3

    Article  PubMed  Google Scholar 

  10. Goldring MB, Goldring SR (2010) Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci 1192:230–237. https://doi.org/10.1111/j.1749-6632.2009.05240.x

    Article  CAS  PubMed  Google Scholar 

  11. Li G, Yin J, Gao J, Cheng TS, Pavlos NJ, Zhang C, Zheng MH (2013) Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes. Arthritis Res Ther 15(6):223. https://doi.org/10.1186/ar4405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bi HY (2002) Reexamination on histomorphology of necrosis of trabecula bones in Kashin-Beck disease. Endemic Dis Bull 17(1):5–7

    Google Scholar 

  13. Li W, Hirvasniemi J, Guo X, Saarakkala S, Lammi MJ (2018) Comparison of bone texture between normal individuals and patients with Kashin-Beck disease from plain radiographs in knee. Sci Rep 8(1):17510. https://doi.org/10.1038/s41598-018-35552-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yoon JH, Abdelmohsen K, Gorospe M (2014) Functional interactions among microRNAs and long noncoding RNAs. Semin Cell Dev Biol 34:9–14. https://doi.org/10.1016/j.semcdb.2014.05.015

    Article  CAS  PubMed  Google Scholar 

  15. Prasadam I, Batra J, Perry S, Gu W, Crawford R, Xiao Y (2016) Systematic identification, characterization and target gene analysis of microRNAs involved in osteoarthritis subchondral bone pathogenesis. Calcif Tissue Int 99(1):43–55. https://doi.org/10.1007/s00223-016-0125-7

    Article  CAS  PubMed  Google Scholar 

  16. Duan C, Guo X, Zhang XD, Yu HJ, Yan H, Gao Y, Ma WJ, Gao ZQ, Xu P, Lammi M (2010) Comparative analysis of gene expression profiles between primary knee osteoarthritis and an osteoarthritis endemic to Northwestern China, Kashin-Beck disease. Arthritis Rheum 62(3):771–780. https://doi.org/10.1002/art.27282

    Article  PubMed  Google Scholar 

  17. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M et al (1986) Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagno Ther Criteria Committee Am Rheum Assoc Arthritis Rheum 29(8):1039–1049

    CAS  Google Scholar 

  18. Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16(4):494–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4(2):249–264. https://doi.org/10.1093/biostatistics/4.2.249

    Article  PubMed  Google Scholar 

  20. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  21. Wu W, He A, Wen Y, Xiao X, Hao J, Zhang F, Guo X (2017) Comparison of microRNA expression profiles of Kashin-Beck disease, osteoarthritis and rheumatoid arthritis. Sci Rep 7(1):540. https://doi.org/10.1038/s41598-017-00522-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang W, Yu Y, Hao J, Wen Y, Han J, Hou W, Liu R, Zhao B, He A, Li P, Fan Q, Wu C, Wang S, Wang X, Ning Y, Guo X, Zhang F (2017) Genome-wide DNA methylation profiling of articular cartilage reveals significant epigenetic alterations in Kashin-Beck disease and osteoarthritis. Osteoarthr Cartil 25(12):2127–2133. https://doi.org/10.1016/j.joca.2017.08.002

    Article  CAS  Google Scholar 

  23. Fu Q, Cao J, Renner JB, Jordan JM, Caterson B, Duance V, Luo M, Kraus VB (2015) Radiographic features of hand osteoarthritis in adult Kashin-Beck disease (KBD): the Yongshou KBD study. Osteoarthr Cartil 23(6):868–873. https://doi.org/10.1016/j.joca.2015.01.009

    Article  CAS  Google Scholar 

  24. Wu J, Huang J, Wang W, Xu J, Yin M, Cheng N, Yin J (2017) Long non-coding RNA Fer-1-like protein 4 acts as a tumor suppressor via miR-106a-5p and predicts good prognosis in hepatocellular carcinoma. Cancer Biomark 20(1):55–65. https://doi.org/10.3233/cbm-170090

    Article  CAS  PubMed  Google Scholar 

  25. Jili S, Eryong L, Lijuan L, Chao Z (2016) RUNX3 inhibits laryngeal squamous cell carcinoma malignancy under the regulation of miR-148a-3p/DNMT1 axis. Cell Biochem Funct 34(8):597–605. https://doi.org/10.1002/cbf.3233

    Article  CAS  PubMed  Google Scholar 

  26. Monteleone NJ, Lutz CS (2017) miR-708-5p: a microRNA with emerging roles in cancer. Oncotarget 8(41):71292–71316. https://doi.org/10.18632/oncotarget.19772

    Article  PubMed  PubMed Central  Google Scholar 

  27. Jia J, Feng X, Xu W, Yang S, Zhang Q, Liu X, Feng Y, Dai Z (2014) MiR-17-5p modulates osteoblastic differentiation and cell proliferation by targeting SMAD7 in non-traumatic osteonecrosis. Exp Mol Med 46:e107. https://doi.org/10.1038/emm.2014.43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhang Y, Gao Y, Cai L, Li F, Lou Y, Xu N, Kang Y, Yang H (2017) MicroRNA-221 is involved in the regulation of osteoporosis through regulates RUNX2 protein expression and osteoblast differentiation. Am J Transl Res 9(1):126–135

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Shen PF, Qu YX, Wang B, Xu JD, Wei K, Xie ZK, Ma Y (2017) miR-30a-5p promotes the apoptosis of chondrocytes in patients with osteoarthritis by targeting protein kinase B. Zhonghua Yi Xue Za Zhi 97(39):3079–3084. https://doi.org/10.3760/cma.j.issn.0376-2491.2017.39.008

    Article  CAS  PubMed  Google Scholar 

  30. Tornero-Esteban P, Rodriguez-Rodriguez L, Abasolo L, Tome M, Lopez-Romero P, Herranz E, Gonzalez MA, Marco F, Moro E, Fernandez-Gutierrez B, Lamas JR (2015) Signature of microRNA expression during osteogenic differentiation of bone marrow MSCs reveals a putative role of miR-335-5p in osteoarthritis. BMC Musculoskelet Disord 16:182. https://doi.org/10.1186/s12891-015-0652-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Desjardin C, Vaiman A, Mata X, Legendre R, Laubier J, Kennedy SP, Laloe D, Barrey E, Jacques C, Cribiu EP, Schibler L (2014) Next-generation sequencing identifies equine cartilage and subchondral bone miRNAs and suggests their involvement in osteochondrosis physiopathology. BMC Genomics 15:798. https://doi.org/10.1186/1471-2164-15-798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lin C, Shao Y, Zeng C, Zhao C, Fang H, Wang L (2018) Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post-traumatic osteoarthritis. J Cell Physiol 233(8):6135–6147. https://doi.org/10.1002/jcp.26460

    Article  CAS  PubMed  Google Scholar 

  33. Du XA, Wang HM, Dai XX, Kou Y, Wu RP, Chen Q, Cao JL, Mo XY, Xiong YM (2015) Role of selenoprotein S (SEPS1) -105G>A polymorphisms and PI3K/Akt signaling pathway in Kashin-Beck disease. Osteoarthr Cartil 23(2):210–216. https://doi.org/10.1016/j.joca.2014.11.017

    Article  CAS  Google Scholar 

  34. Sharma AR, Jagga S, Lee SS, Nam JS (2013) Interplay between cartilage and subchondral bone contributing to pathogenesis of osteoarthritis. Int J Mol Sci 14(10):19805–19830. https://doi.org/10.3390/ijms141019805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Liou SF, Hsu JH, Chu HC, Lin HH, Chen IJ, Yeh JL (2015) KMUP-1 promotes osteoblast differentiation through cAMP and cGMP pathways and signaling of BMP-2/Smad1/5/8 and Wnt/beta-catenin. J Cell Physiol 230(9):2038–2048. https://doi.org/10.1002/jcp.24904

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the National Natural Scientific Foundation of China (NO. 81472924 and 81620108026) and the Fundamental Research Funds for the Central Universities (NO. xjj2018154).

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Author notes

  1. Guang-Hui Zhao and Lei Yang contributed equally to this work and should be considered as co-first authors.

Authors and Affiliations

  1. Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, People’s Republic of China

    Guang-Hui Zhao, Lei Yang, Mikko J. Lammi & Xiong Guo

  2. School of Nursing, Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China

    Lei Yang

  3. Department of Integrative Medical Biology, University of Umeå, Umeå, Sweden

    Mikko J. Lammi

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  1. Guang-Hui Zhao
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Corresponding authors

Correspondence to Mikko J. Lammi or Xiong Guo.

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The ethics committee of Xi’an Jiaotong University has approved this study, and informed consent was obtained from all individual participants included in the study.

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Zhao, GH., Yang, L., Lammi, M.J. et al. A preliminary analysis of microRNA profiles in the subchondral bone between Kashin-Beck disease and primary knee osteoarthritis. Clin Rheumatol 38, 2637–2645 (2019). https://doi.org/10.1007/s10067-019-04580-8

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