Abstract

Research Article

Differentiation of bone marrow cells in arthritic mice with decreased complement activity

Petya Ganova and Nina Ivanovska*

Published: 31 December, 2018 | Volume 2 - Issue 1 | Pages: 028-038

There is evidence that complement components induce cell migration in mesenchymal stem cells and regulate cytokine production in osteoblastic cells thus playing a regulatory role in normal bone formation. The aim of the present study was to investigate the involvement of complement system in the differentiation of bone marrow cells in complement-depleted model of rheumatoid arthritis (RA). Arthritis was induced by intraarticular injection of zymosan in cobra venom factor (CVF)-treated mice depleted of functional complement. The expression of different markers by bone marrow [1], on fibroblasts (CD29), mesenchymal cells (CD105), dendritic cells (CD14, CD86), osteoclasts (CD265), cells expressing Dectin1 (CD369) and megakaryocytes (CD62P) was determined by flowcytometry. The lack of functional complement activity at the point of arthritis initiation (day 3) lead to an increase of fibroblast and megakaryocyte populations, to a decrease of mature and dectin1 positive populations, while the number of mesenchymal cells was not changed, all compared to arthritic mice. Immunohistochemical staining showed that low complement activity diminished arthritis-induced generation of megakaryocytes and platelets in BM. Chronic inflammation during erosive conditions such as rheumatoid arthritis, leads to dysregulated differentiation and prolifеration of bone cells, inflammation of synovial membrane and bone marrow, and degradation of cartilage and bone. Present results point that the lack of functional complement changed the ratio between different cell populations that can be used for determining the development and stage of rheumatoid arthritis and can help finding of new therapeutic approaches.

Read Full Article HTML DOI: 10.29328/journal.icci.1001006 Cite this Article Read Full Article PDF

Keywords:

Zymosan-induced arthritis; Dendritic cells; Mesnchymal cells; Fibroblasts; Megakaryocytes

References

  1. Kawai T, Matsuyama T, Hosokawa Y, Makihira S, Seki M, et al. B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am J Pathol. 2006; 169: 987-998. Ref.:.: https://goo.gl/Axuf7P
  2. Okroj M, Heinegård D, Holmdahl R, Blom AM. Rheumatoid arthritis and the complement system. Ann Med. 2007; 39: 517-530. Ref.: https://goo.gl/T4hFxH
  3. Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010; 11: 785-797. Ref.: https://goo.gl/L9XmUX
  4. Konttinen YT, Ceponis A, Meri S, Vuorikoski A, Kortekangas P, et al. Complement in acute and chronic arthritides: assessment of C3c, C9, and protectin (CD59) in synovial membrane. Ann Rheum Dis. 1996; 55: 888-894. Ref.: https://goo.gl/QcXZaA
  5. Neumann E, Barnum SR, Tarner IH, Echols J, Fleck M, et al. Local production of complement proteins in rheumatoid arthritis synovium. Arthritis Rheum. 2002; 46: 934-945. Ref.: https://goo.gl/VzNUpi
  6. O'Gradaigh D, Compston JE. T-cell involvement in osteoclast biology: implications for rheumatoid bone erosion. Rheumatology (Oxford). 2004; 43: 122-130. Ref.: https://goo.gl/pe25MS
  7. Sato T, Abe E, Jin CH, Hong MH, Katagiri T, et al. The biological roles of the third component of complement in osteoclast formation. Endocrinology. 1993; 133: 397-404. Ref.: https://goo.gl/adpH2m
  8. Wang X, Wang Y, Gou W, Lu Q, Peng J, et al. Role of mesenchymal stem cells in bone regeneration and fracture repair: a review. Int Orthop. 2013; 37: 2491-2498. Ref.: https://goo.gl/sy5tJ5
  9. Farini A, Sitzia C1, Erratico S1, Meregalli M1, Torrente Y. Clinical applications of mesenchymal stem cells in chronic diseases. Stem Cells Int. 2014; 2014: 306573. Ref.: https://goo.gl/uvRvMg
  10. Kristjánsson B, Honsawek S. Mesenchymal stem cells for cartilage regeneration in osteoarthritis. World J Orthop. 2017; 8: 674-680. Ref.: https://goo.gl/RVv2Nz
  11. Duff SE, Li C, Garland JM, Kumar S. CD105 is important for angiogenesis: evidence and potential applications, FASEB J. 2003; 17: 984-992. Ref.: https://goo.gl/UkUM2y
  12. Lutzky V, Hannawi S, Thomas R. Cells of the synovium in rheumatoid arthritis. Dendritic cells. Arthritis Res Ther. 2007; 9: 219. Ref.: https://goo.gl/ung6ed
  13. Sallusto F, Lanzavecchia A. Mobilizing dendritic cells for tolerance, priming, and chronic inflammation. J Exp Med. 1999; 189: 611-614. Ref.: https://goo.gl/7Sfk6N
  14. Apostolopoulos V, Thalhammer T, Tzakos AG, Stojanovska L. Targeting antigens to dendritic cell receptors for vaccine development. J Drug Deliv. 2013; 2013: 869718 Ref.: https://goo.gl/B5kUTb
  15. LeibundGut-Landmann S, Gross O, Robinson MJ, Osorio F, Slack EC, et al. Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol. 2007; 8: 630-638. Ref.: https://goo.gl/jnmsnS
  16. Gerosa F, Baldani-Guerra B, Lyakh LA, Batoni G, Esin S,, et al. Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells. J Exp Med. 2008; 205: 1447-1461. Ref.: https://goo.gl/JZgKad
  17. Nakeff A, Maat B. Separation of megakaryocytes from mouse bone marrow by velocity sedimentation. Blood. 1974; 43: 591-595. Ref.: https://goo.gl/8WZ9Qp
  18. Zou Z, Schmaier AA, Cheng L, Mericko P, Dickeson SK, et al. Negative regulation of activated alpha-2 integrins during thrombopoiesis. Blood. 2009; 113: 6428-6439. Ref.: https://goo.gl/AQkrCF
  19. Arbesu I, Bucsaiova M, Fischer MB, Mannhalter C. Platelet-borne complement proteins and their role in platelet-bacteria interactions. J Thromb Haemost. 2016; 14: 2241-2252. Ref.: https://goo.gl/BZyCPZ
  20. Teitelbaum SL. Bone resorption by osteoclasts. Science. 2000; 289: 1504-1508. Ref.: https://goo.gl/o1FPZg
  21. Boyce BF. Advances in the regulation of osteoclasts and osteoclast functions. J Dent Res. 2013; 92: 860-867. Ref.: https://goo.gl/rFcmvG
  22. Teitelbaum SL. The osteoclast and its unique cytoskeleton. Ann N Y Acad Sci. 2011; 1240: 14-17. Ref.: https://goo.gl/dDERHq
  23. Belenska-Todorova L, Gyurkovska V, Ivanovska N. How complement activation influences the development of chronic synovitis in a mouse model of rheumatoid arthritis. Scand J Rheumatol. 2016; 45: 13-22. Ref.: https://goo.gl/tjJ7us
  24. Ganova P, Gyurkovska V, Belenska-Todorova L, Ivanovska N. Functional complement activity is decisive for the development of chronic synovitis, osteophyte formation and processes of cell senescence in zymosan-induced arthritis. Immunol Lett. 2017; 190: 213-220. Ref.: https://goo.gl/6jwmK1
  25. Buckley CD, Pilling D, Lord JM, Akbar AN, Scheel-Toellner D, et al. Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation. Trends Immunol. 2001; 22: 199-204. Ref.: https://goo.gl/w2rV1j
  26. Müller-Ladner U, Pap T, Gay RE, Neidhart M, Gay S. Mechanisms of disease: the molecular and cellular basis of joint destruction in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2005; 1: 102-110. Ref.: https://goo.gl/Nv5BMj
  27. Arend WP, Mehta G, Antonioli AH, Takahashi M, Takahashi K, et al. Roles of adipocytes and fibroblasts in activation of the alternative pathway of complement in inflammatory arthritis in mice. J Immunol. 2013; 190: 6423-6433. Ref.: https://goo.gl/7B9V1x
  28. Guc D, Gulati P, Lemercier C, Lappin D, Birnie GD, et al. Expression of the components and regulatory proteins of the alternative complement pathway and the membrane attack complex in normal and diseased synovium. Rheumatol Int. 1993; 13: 139-146. Ref.: https://goo.gl/nwLmWj
  29. Lefèvre S, Knedla A, Tennie C, Kampmann A, Wunrau C, et al. Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat Med. 2009; 15: 1414-1420. Ref.: https://goo.gl/ukVcP8
  30. Leung BP, Conacher M, Hunter D, McInnes IB, Liew FY, et al. A novel dendritic cell-induced model of erosive inflammatory arthritis: distinct roles for dendritic cells in T cell activation and induction of local inflammation. J Immunol. 2002; 169: 7071-7077. Ref.: https://goo.gl/ukyXSt
  31. Thomas R, Davis LS, Lipsky PE Rheumatoid synovium is enriched in mature antigen-presenting dendritic cells. J Immunol. 1994; 152: 2613-2623. Ref.: https://goo.gl/2E4Wfp
  32. Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, et al. RANK is essential for osteoclast and lymph node development. Genes Dev. 1999; 13: 2412-2424. Ref.: https://goo.gl/M5AoWD
  33. Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999; 397: 315-323. Ref.: https://goo.gl/VgBFef
  34. Lubberts E, Koenders MI, van den Berg WB The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal models. Arthritis Res Ther. 2005; 7: 29-37. Ref.: https://goo.gl/EXBJVk
  35. Wysoczynski M, Kucia M, Ratajczak J, Ratajczak MZ. Cleavage fragments of the third complement component (C3) enhance stromal derived factor-1 (SDF-1)-mediated platelet production during reactive post bleeding thrombocytosis. Leukemia. 2007; 21: 973-982. https://goo.gl/U1ZLia
  36. Ciovacco WA, Cheng YH, Horowitz MC, Kacena MA. Immature and mature megakaryocytes enhance osteoblast proliferation and inhibit osteoclast formation. J Cell Biochem. 2010; 109: 774-781. Ref.: https://goo.gl/j58HZn
  37. Underhill DM. Macrophage recognition of zymosan particles. J Endotoxin Res. 2003; 9: 176-180. Ref.: https://goo.gl/Qof2oK
  38. Granucci F, Feau S, Angeli V, Trottein F, Ricciardi-Castagnoli P. Early IL-2 production by mouse dendritic cells is the result of microbial-induced priming. J Immunol. 2003; 170: 5075-5081. Ref.: https://goo.gl/CRn9Es

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