Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Upregulation of miR-23b Enhances the Autologous Therapeutic Potential for Degenerative Arthritis by Targeting PRKACB in Synovial Fluid-Derived Mesenchymal Stem Cells from Patients

  • Ham, Onju (Cardiovascular Research Institute, Yonsei University College of Medicine) ;
  • Lee, Chang Youn (Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University) ;
  • Song, Byeong-Wook (Cardiovascular Research Institute, Yonsei University College of Medicine) ;
  • Lee, Se-Yeon (Cardiovascular Research Institute, Yonsei University College of Medicine) ;
  • Kim, Ran (Department of Biology Education, College of Education, Pusan National University) ;
  • Park, Jun-Hee (Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University) ;
  • Lee, Jiyun (Cardiovascular Research Institute, Yonsei University College of Medicine) ;
  • Seo, Hyang-Hee (Cardiovascular Research Institute, Yonsei University College of Medicine) ;
  • Lee, Chae Yoon (Department of Biology Education, College of Education, Pusan National University) ;
  • Chung, Yong-An (Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine) ;
  • Maeng, Lee-So (Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine) ;
  • Lee, Min Young (Department of Molecular Physiology, College of Pharmacy, Kyungpook National University) ;
  • Kim, Jongmin (Department of Life Systems, Sookmyung Women's University) ;
  • Hwang, Jihwan (Department of Microbiology, College of Natural Science, Pusan National University) ;
  • Woo, Dong Kyun (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University) ;
  • Chang, Woochul (Department of Biology Education, College of Education, Pusan National University)
  • Received : 2014.02.03
  • Accepted : 2014.05.22
  • Published : 2014.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

The use of synovial fluid-derived mesenchymal stem cells (SFMSCs) obtained from patients with degenerative arthropathy may serve as an alternative therapeutic strategy in osteoarthritis (OA) and rheumatoid arthritis (RA). For treatment of OA and RA patients, autologous transplantation of differentiated MSCs has several beneficial effects for cartilage regeneration including immunomodulatory activity. In this study, we induced chondrogenic differentiation of SFMSCs by inhibiting protein kinase A (PKA) with a small molecule and microRNA (miRNA). Chondrogenic differentiation was confirmed by PCR and immunocytochemistry using probes specific for aggrecan, the major cartilaginous proteoglycan gene. Absorbance of alcian blue stain to detect chondrogenic differentiation was increased in H-89 and/or miRNA-23b-transfected cells. Furthermore, expression of matrix metalloproteinase (MMP)-9 and MMP-2 was decreased in treated1 cells. Therefore, differentiation of SFMSCs into chondrocytes through inhibition of PKA signaling may be a therapeutic option for OA or RA patients.

Keywords

References

  1. Andersen, D.C., Kortesidis, A., Zannettino, A.C., Kratchmarova, I., Chen, L., Jensen, O.N., Teisner, B., Gronthos, S., Jensen, C.H., and Kassem, M. (2011). Development of novel monoclonal antibodies that define differentiation stages of human stromal (mesenchymal) stem cells. Mol. Cells 32, 133-142. https://doi.org/10.1007/s10059-011-2277-7
  2. Bagga, S., Bracht, J., Hunter, S., Massirer. K., Holtz, J., Eachus. R., and Pasquinelli, A.E. (2005). Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 122, 553-563. https://doi.org/10.1016/j.cell.2005.07.031
  3. Barry, F.P., and Murphy, J.M. (2004). Mesenchymal stem cells: clinical applications and biological characterization. Int. J. Biochem. Cell. Biol. 36, 568-584. https://doi.org/10.1016/j.biocel.2003.11.001
  4. Chang, W., Park, S.I., Jun, S.Y., Lee, E.J., Ham, H.J., Bae, Y.J., Kim, R., Park, M.S., Chung, Y.A., Im, N., et al. (2013). Therapeutic potential of autologous mesenchymal stem cells derived from synovial fluid in patients with degenerative arthritis. Animal Cells Syst. 17, 315-324. https://doi.org/10.1080/19768354.2013.832705
  5. Cohen, P. (1999). The development and therapeutic potential of protein kinase inhibitors. Curr. Opin. Chem. Biol. 3, 459-465. https://doi.org/10.1016/S1367-5931(99)80067-2
  6. Davies, S.P., Reddy, H., Caivano, M., and Cohen, P. (2000). Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 351, 95-105. https://doi.org/10.1042/0264-6021:3510095
  7. De Ugarte, D.A., Morizono, K., Elbarbary, A., Alfonso, Z., Zuk, P.A., Zhu, M., Dragoo, J.L., Ashjian, P., Thomas, B., Benhaim, P., et al. (2003). Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 174, 101-109. https://doi.org/10.1159/000071150
  8. Dunn, W., DuRaine, G., and Reddi, A.H. (2009). Profiling micro-RNA expression in bovine articular cartilage and implications for mechanotransduction. Arthritis Rheum. 60, 2333-2339. https://doi.org/10.1002/art.24678
  9. Friedenstein, A.J. (1980). Stromal mechanisms of bone marrow: cloning in vitro and retransplantation in vivo. Haematol. Blood Transfus. 25, 19-29.
  10. Giraldez, A.J., Mishima, Y., Rihel, J., Grocock, R.J., Van Dongen, S., Inoue, K., Enright, A.J., and Schier, A.F. (2006). Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312, 75-79. https://doi.org/10.1126/science.1122689
  11. Goldring, M.B., Tsuchimochi, K., and Ijiri, K. (2006). The control of chondrogenesis. J. Cell. Biochem. 97, 33-44. https://doi.org/10.1002/jcb.20652
  12. Guerit, D., Philipot, D., Chuchana, P., Toupet, K., Brondello, J.M., Mathieu, M., Jorgensen, C., and Noel D. (2013). Sox9-regulated miRNA-574-3p inhibits chondrogenic differentiation of mesenchymal stem cells. PLoS One 8, e62582. https://doi.org/10.1371/journal.pone.0062582
  13. Ham, O., Song, B.W., Lee, S.Y., Choi, E., Cha, M.J., Lee, C.Y., Park, J.H., Kim, I.K., Chang, W., Lim, S., et al. (2012). The role of microRNA-23b in the differentiation of MSC into chondrocyte by targeting protein kinase A signaling. Biomaterials 33, 4500-4507. https://doi.org/10.1016/j.biomaterials.2012.03.025
  14. Hong, E., and Reddi, A.H. (2013). Dedifferentiation and redifferentiation of articular chondrocytes from surface and middle zones: changes in microRNAs-221/-222,-140, and -143/145 expression. Tissue Eng. Part A 19, 1015-1022. https://doi.org/10.1089/ten.tea.2012.0055
  15. Horwitz, E.M., Prockop, D.J., Fitzpatrick, L.A., Koo, W.W., Gordon, P.L., Neel, M., Sussman, M., Orchard, P., Marx, J.C., Pyeritz, R.E., et al. (1999). Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfect. Nat. Med. 5, 309-313. https://doi.org/10.1038/6529
  16. Hwang, K.C., Kim, J.Y., Chang, W., Kim, D.S., Lim, S., Kang, S.M., Song, B.W., Ha, H.Y., Huh, Y.J., Choi, I.G., et al. (2008) Chemicals that modulate stem cell differentiation. Proc. Natl. Acad. Sci. USA 105, 7467-7471. https://doi.org/10.1073/pnas.0802825105
  17. Iwata, H., Ono, S., Sato, K., Sato, T., and Kawamura, M. (1993). Bone morphogenetic protein-induced muscle- and synovium-derived cartilage differentiation in vitro. Clin. Orthop. Relat. Res. 296, 295-300.
  18. Jin, H.L., Kim, J.S., Kim, Y.J., Kim, S.J., Broxmeyer, H.E., and Kim, K.S. (2012). Dynamic expression of specific miRNAs during erythroid differentiation of human embryonic stem cells. Mol. Cells 34, 177-183. https://doi.org/10.1007/s10059-012-0090-6
  19. Jones, E.A., English, A., Henshaw, K., Kinsey, S.E., Markham, A.F., Emery, P., and McGonagle, D. (2004). Enumeration and phenotypic characterization of synovial fluid multipotential mesenchymal progenitor cells in inflammatory and degenerative arthritis. Arthritis Rheum. 50, 817-827. https://doi.org/10.1002/art.20203
  20. Jones, E.A., Crawford, A., English, A., Henshaw, K., Mundy, J., Corscadden, D., Chapman, T., Emery, P., Hatton, P., and McGonagle, D. (2008). Synovial fluid mesenchymal stem cells in health and early osteoarthritis: detection and functional evaluation at the single-cell level. Arthritis Rheum. 58, 1731-1740. https://doi.org/10.1002/art.23485
  21. Jones, E., Churchman, S.M., English, A., Buch, M.H., Horner, E.A., Burgoyne, C.H., Reece, R., Kinsey, S., Emery, P., and McGonagle, D. (2010). Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level. Ann. Rheum. Dis. 69, 450-457. https://doi.org/10.1136/ard.2008.106435
  22. Karlsen, T.A., Jakobsen, R.B, Mikkelsen, T.S., and Brinchmann, J.E. (2014). microRNA-140 targets RALA and regulates chondrogenic differentiation of human mesenchymal stem cells by translational enhancement of SOX9 and ACAN. Stem Cells Dev. 23, 290-304. https://doi.org/10.1089/scd.2013.0209
  23. Kang, W.J., Cho, Y.L., Chae, J.R., Lee, J.D., Choi, K.J., and Kim, S. (2011). Molecular beacon-based bioimaging of multiple microRNAs during myogenesis. Biomaterials 32, 1915-1922. https://doi.org/10.1016/j.biomaterials.2010.11.007
  24. Kobayashi, T., Lu, J., Cobb, B.S., Rodda, S.J., McMahon, A.P., Schipani, E., Merkenschlager, M., and Kronenberg, H.M. (2008). Dicer-dependent pathways regulate chondrocyte proliferation and differentiation. Proc. Natl. Acad. Sci. USA 105, 1949-1954. https://doi.org/10.1073/pnas.0707900105
  25. Koga, H., Muneta, T., Nagase, T., Nimura, A., Ju, Y.J., Mochizuki, T., and Sekiya, I. (2008). Comparison of mesenchymal tissues-derived stem cells for in vivo chondrogenesis: suitable conditions for cell therapy of cartilage defects in rabbit. Cell Tissue Res. 333, 207-215. https://doi.org/10.1007/s00441-008-0633-5
  26. Lee, W.J., Park, S.E., and Rah, D.K. (2011). Effects of hepatocyte growth factor on collagen synthesis and matrix metalloproteinase production in keloids. J. Korean Med. Sci. 26, 1081-1086. https://doi.org/10.3346/jkms.2011.26.8.1081
  27. Lee, D.H., Sonn, C.H., Han, S.B., Oh, Y., Lee, K.M., and Lee, S.H. (2012). Synovial fluid $CD34^-\;CD44^+\;CD90^+$ mesenchymal stem cell levels are associated with the severity of primary knee osteoarthritis. Osteoarthritis Cartilage 20, 106-109. https://doi.org/10.1016/j.joca.2011.11.010
  28. Lin, E.A., Kong, L., Bai, X.H., Luan, Y., and Liu, C.J. (2009). miR-199a, a bone morphogenic protein 2-responsive MicroRNA, regulates chondrogenesis via direct targeting to Smad1. J. Biol. Chem. 284, 11326-11335. https://doi.org/10.1074/jbc.M807709200
  29. Lohmander, L.S., and Roos, E.M. (2007). Clinical update: treating osteoarthritis. Lancet 370, 2082-2084. https://doi.org/10.1016/S0140-6736(07)61879-0
  30. Morito, T., Muneta, T., Hara, K., Ju, Y.J., Mochizuki, T., Makino, H., Umezawa, A., and Sekiya, I. (2008). Synovial fluid-derived mesenchymal stem cells increase after intra-articular ligament injury in humans. Rheumatology 47, 1137-1143. https://doi.org/10.1093/rheumatology/ken114
  31. Myers, T.J., Granero-Molto, F., Longobardi, L., Li, T., Yan, Y., and Spagnoli, A. (2010). Mesenchymal stem cells at the intersection of cell and gene therapy. Exp. Opin. Biol. Ther. 10, 1663-1679. https://doi.org/10.1517/14712598.2010.531257
  32. Nakamura, Y., Inloes, J.B., Katagiri, T., and Kobayashi, T. (2011). Chondrocyte-specific microRNA-140 regulates endochondral bone development and targets Dnpep to modulate bone morphogenetic protein signaling. Mol. Cell Biol. 31, 3019-3028. https://doi.org/10.1128/MCB.05178-11
  33. Nishimura, K., Solchaga, L.A., Caplan, A.I., Yoo, J.U., Goldberg, V.M., and Johnstone, B., (1999). Chondroprogenitor cells of synovial tissue. Arthritis Rheum. 42, 2631-2637. https://doi.org/10.1002/1529-0131(199912)42:12<2631::AID-ANR18>3.0.CO;2-H
  34. Olivotto, E, Otero, M., Astolfi, A., Platano, D., Facchini, A., Pagani, S., Flamigni, F., Facchini, A., Goldring, M.B., Borzi, R.M., et al. (2013). $IKK{\alpha}$/CHUK regulates extracellular matrix remodeling independent of its kinase activity to facilitate articular chondrocyte differentiation. PLoS One 8, e73024. https://doi.org/10.1371/journal.pone.0073024
  35. Olsen, B.R., Reginato, A.M., and Wang, W. (2000). Bone development. Annu. Rev. Cell Dev. Biol. 16, 191-220. https://doi.org/10.1146/annurev.cellbio.16.1.191
  36. Pelttari, L., Steck, E., and Richter, W. (2008). The use of mesenchymal stem cells for chondrogenesis. Injury 39, S58-S65. https://doi.org/10.1016/j.injury.2008.01.038
  37. Prockop, D.J., Azizi, S.A., Colter, D., Digirolamo, C., Kopen, G., and Phinney, D.G. (2000). Potential use of stem cells from bone marrow to repair the extracellular matrix and the central nervous system. Biochem. Soc. Trans. 28, 341-345. https://doi.org/10.1042/0300-5127:0280341
  38. Sakaguchi, Y., Sekiya, I., Yagishita, K., and Muneta, T. (2005). Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum. 52, 2521-2529. https://doi.org/10.1002/art.21212
  39. Segawa, Y., Muneta, T., Makino, H., Nimura, A., Mochizuki, T., Ju, Y.J., Ezura, Y., Umezawa, A., and Sekiya, I. (2009). Mesenchymal stem cells derived from synovium, meniscus, anterior cruciate ligament, and articular chondrocytes share similar gene expression profiles. J. Orthop. Res. 27, 435-441. https://doi.org/10.1002/jor.20786
  40. Sekiya, I., Ojima, M., Suzuki, S., Yamaga, M., Horie, M., Koga, H., Tsuji, K., Miyaguchi, K., Ogishima, S., Tanaka, H., et al. (2012). Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis. J. Orthop. Res. 30, 943-949. https://doi.org/10.1002/jor.22029
  41. Sherriff-Tadano, R., Ohta, A., Morito, F., Mitamura, M., Haruta, Y., Koarada, S., Tada, Y., Nagasawa, K., and Ozaki, I. (2006). Antifibrotic effects of hepatocyte growth factor on scleroderma fibroblasts and analysis of its mechanism. Mod. Rheumatol. 16, 364-371. https://doi.org/10.3109/s10165-006-0525-z
  42. Vinatier, C., Bouffi, C., Merceron, C., Gordeladze, J., Brondello, J.M., Jorgensen, C., Weiss, P., Guicheux, J., and Noel, D. (2009). Cartilage tissue engineering: towards a biomaterial-assisted mesenchymal stem cell therapy. Curr. Stem Cell Res. Ther. 4, 318-329. https://doi.org/10.2174/157488809789649205
  43. Wu, C.W., Tchetina, E.V., Mwale, F., Hasty, K., Pidoux, I., Reiner, A., Chen, J., Van Wart, H.E, and Poole, A.R. (2002). Proteolysis involving matrix metalloproteinase 13 (collagenase-3) is required for chondrocyte differentiation that is associated with matrix mineralization. J. Bone Miner Res.17, 639-651. https://doi.org/10.1359/jbmr.2002.17.4.639
  44. Wu, L., Fan, J., and Belasco, J.G. (2006). MicroRNAs direct rapid deadenylation of mRNA. Proc. Natl. Acad. Sci. USA 103, 4034-4039. https://doi.org/10.1073/pnas.0510928103
  45. Xiong, X., Kang, X., Zheng, Y., Yue, S., and Zhu, S. (2013). Identification of loop nucleotide polymorphisms affecting microRNA processing and function. Mol. Cells 36, 518-526. https://doi.org/10.1007/s10059-013-0171-1
  46. Yamaoka, H., Asato, H., Ogasawara, T., Nishizawa, S., Takahashi, T., Nakatsuka, T., Koshima, I., Nakamura, K., Kawaguchi, H., Chung, U.I., et al. (2006). Cartilage tissue engineering using human auricular chondrocytes embedded in different hydrogel materials. J. Biomed. Mater. Res. 78, 1-11.
  47. Yan, C., Wang, Y., Shen, X.Y., Yang, G., Jian, J., Wang, H.S., Chen, G.Q., and Wu, Q. (2011). MicroRNA regulation associated chondrogenesis of mouse MSCs grown on polyhydroxyalkanoates. Biomaterials 32, 6435-6444. https://doi.org/10.1016/j.biomaterials.2011.05.031
  48. Yoshimura, H., Muneta, T., Nimura, A., Yokoyama, A., Koga, H., and Sekiya, I. (2007). Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res. 327, 449-462. https://doi.org/10.1007/s00441-006-0308-z
  49. Zhai, L.J., Zhao, K.Q., Wang, Z.Q., Feng, Y., and Xing, S.C. (2001). Mesenchymal stem cells display different gene expression profiles compared to hyaline and elastic chondrocytes. Int. J. Clin. Exp. Med. 4, 81-90.

Cited by

  1. MicroRNAs’ Involvement in Osteoarthritis and the Prospects for Treatments vol.2015, 2015, https://doi.org/10.1155/2015/236179
  2. Mesenchymal stem cells for the management of inflammation in osteoarthritis: state of the art and perspectives vol.23, pp.11, 2015, https://doi.org/10.1016/j.joca.2015.07.004
  3. The Role of MicroRNAs and Their Targets in Osteoarthritis vol.18, pp.8, 2016, https://doi.org/10.1007/s11926-016-0604-x
  4. Alternative new mesenchymal stem cell source exerts tumor tropism through ALCAM and N-cadherin via regulation of microRNA-192 and -218 vol.427, pp.1-2, 2017, https://doi.org/10.1007/s11010-016-2909-5
  5. MicroRNAs in rheumatoid arthritis vol.34, pp.4, 2015, https://doi.org/10.1007/s10067-015-2898-x
  6. microRNAs in Cartilage Development, Homeostasis, and Disease vol.12, pp.4, 2014, https://doi.org/10.1007/s11914-014-0229-9
  7. miRNA-Regulated Key Components of Cytokine Signaling Pathways and Inflammation in Rheumatoid Arthritis vol.36, pp.3, 2016, https://doi.org/10.1002/med.21384
  8. Deregulation and therapeutic potential of microRNAs in arthritic diseases vol.12, pp.4, 2015, https://doi.org/10.1038/nrrheum.2015.162
  9. Gene therapy for chondral and osteochondral regeneration: is the future now? 2017, https://doi.org/10.1007/s00018-017-2637-3
  10. Enhanced Healing of Rat Calvarial Bone Defects with Hypoxic Conditioned Medium from Mesenchymal Stem Cells through Increased Endogenous Stem Cell Migration via Regulation of ICAM-1 Targeted-microRNA-221 vol.38, pp.7, 2015, https://doi.org/10.14348/molcells.2015.0050
  11. MicroRNAs in Bone Balance and Osteoporosis vol.76, pp.5, 2015, https://doi.org/10.1002/ddr.21260
  12. Therapeutic Potential of Differentiated Mesenchymal Stem Cells for Treatment of Osteoarthritis vol.16, pp.7, 2015, https://doi.org/10.3390/ijms160714961
  13. miRNAs Related to Skeletal Diseases vol.25, pp.17, 2016, https://doi.org/10.1089/scd.2016.0133
  14. A bioinformatic analysis of microRNAs role in osteoarthritis vol.25, pp.8, 2017, https://doi.org/10.1016/j.joca.2017.03.012
  15. Epigenetic aspects of rheumatoid arthritis: contribution of non-coding RNAs vol.46, pp.6, 2017, https://doi.org/10.1016/j.semarthrit.2017.01.003
  16. New Approach for Differentiation of Bone Marrow Mesenchymal Stem Cells Toward Chondrocyte Cells With Overexpression of MicroRNA-140 vol.64, pp.5, 2018, https://doi.org/10.1097/MAT.0000000000000688
  17. Decreased MiR-128-3p alleviates the progression of rheumatoid arthritis by up-regulating the expression of TNFAIP3 vol.38, pp.4, 2018, https://doi.org/10.1042/BSR20180540
  18. The Role of miRNAs in Cartilage Homeostasis vol.16, pp.6, 2015, https://doi.org/10.2174/1389202916666150817203144
  19. Enhanced chondrogenesis differentiation of human induced pluripotent stem cells by MicroRNA-140 and transforming growth factor beta 3 (TGFβ3) vol.52, pp.None, 2018, https://doi.org/10.1016/j.biologicals.2018.01.005
  20. Dietary exosome-miR-23b may be a novel therapeutic measure for preventing Kashin-Beck disease vol.15, pp.4, 2018, https://doi.org/10.3892/etm.2018.5885
  21. Senescence cell-associated extracellular vesicles serve as osteoarthritis disease and therapeutic markers vol.4, pp.7, 2014, https://doi.org/10.1172/jci.insight.125019
  22. Therapeutic Potential of Mesenchymal Stromal Stem Cells in Rheumatoid Arthritis: a Systematic Review of In Vivo Studies vol.16, pp.2, 2014, https://doi.org/10.1007/s12015-020-09954-z
  23. Adipose-Derived Mesenchymal Stromal Cells Treated with Interleukin 1 Beta Produced Chondro-Protective Vesicles Able to Fast Penetrate in Cartilage vol.10, pp.5, 2021, https://doi.org/10.3390/cells10051180
  24. Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization vol.29, pp.7, 2014, https://doi.org/10.1016/j.joca.2021.04.006