Skip to main content

Advertisement

SpringerLink
Log in

HMGB proteins and arthritis

  • Review Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

The high-mobility group box (HMGB) family includes four members: HMGB1, 2, 3 and 4. HMGB proteins have two functions. In the nucleus, HMGB proteins bind to DNA in a DNA structure-dependent but nucleotide sequence-independent manner to function in chromatin remodeling. Extracellularly, HMGB proteins function as alarmins, which are endogenous molecules released upon tissue damage to activate the immune system. HMGB1 acts as a late mediator of inflammation and contributes to prolonged and sustained systemic inflammation in subjects with rheumatoid arthritis. By contrast, Hmgb2 −/− mice represent a relevant model of aging-related osteoarthritis (OA), which is associated with the suppression of HMGB2 expression in cartilage. Hmgb2 mutant mice not only develop early-onset OA but also exhibit a specific phenotype in the superficial zone (SZ) of articular cartilage. Given the similar expression and activation patterns of HMGB2 and β-catenin in articular cartilage, the loss of these pathways in the SZ of articular cartilage may lead to altered gene expression, cell death and OA-like pathogenesis. Moreover, HMGB2 regulates chondrocyte hypertrophy by mediating Runt-related transcription factor 2 expression and Wnt signaling. Therefore, one possible mechanism explaining the modulation of lymphoid enhancer binding factor 1 (LEF1)-dependent transactivation by HMGB2 is that a differential interaction between HMGB2 and nuclear factors affects the transcription of genes containing LEF1-responsive elements. The multiple functions of HMGB proteins reveal the complex roles of these proteins as innate and endogenous regulators of inflammation in joints and their cooperative roles in cartilage hypertrophy as well as in the maintenance of joint tissue homeostasis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Stros M. HMGB proteins: interactions with DNA and chromatin. Biochim Biophys Acta. 2010;1799:101–13.

    Article  CAS  PubMed  Google Scholar 

  2. Bustin M. Regulation of DNA-dependent activities by the functional motifs of the high-mobility-group chromosomal proteins. Mol Cell Biol. 1999;19:5237–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Catena R, Escoffier E, Caron C, Khochbin S, Martianov I, Davidson I. HMGB4, a novel member of the HMGB family, is preferentially expressed in the mouse testis and localizes to the basal pole of elongating spermatids. Biol Reprod. 2009;80:358–66.

    Article  CAS  PubMed  Google Scholar 

  4. Pauken CM, Nagle DL, Bucan M, Lo CW. Molecular cloning, expression analysis, and chromosomal localization of mouse Hmg1-containing sequences. Mamm Genome. 1994;5:91–9.

    Article  CAS  PubMed  Google Scholar 

  5. Ronfani L, Ferraguti M, Croci L, et al. Reduced fertility and spermatogenesis defects in mice lacking chromosomal protein Hmgb2. Development. 2001;128:1265–73.

    CAS  PubMed  Google Scholar 

  6. Vaccari T, Beltrame M, Ferrari S, Bianchi ME. Hmg4, a new member of the Hmg1/2 gene family. Genomics. 1998;49:247–52.

    Article  CAS  PubMed  Google Scholar 

  7. Abraham AB, Bronstein R, Chen EI, et al. Members of the high mobility group B protein family are dynamically expressed in embryonic neural stem cells. Proteome Sci. 2013;11:18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhou Q, Law AC, Rajagopal J, Anderson WJ, Gray PA, Melton DA. A multipotent progenitor domain guides pancreatic organogenesis. Dev Cell. 2007;13:103–14.

    Article  CAS  PubMed  Google Scholar 

  9. Mosevitsky MI, Novitskaya VA, Iogannsen MG, Zabezhinsky MA. Tissue specificity of nucleo-cytoplasmic distribution of HMG1 and HMG2 proteins and their probable functions. Eur J Biochem. 1989;185:303–10.

    Article  CAS  PubMed  Google Scholar 

  10. Muller S, Ronfani L, Bianchi ME. Regulated expression and subcellular localization of HMGB1, a chromatin protein with a cytokine function. J Intern Med. 2004;255:332–43.

    Article  CAS  PubMed  Google Scholar 

  11. Nemeth MJ, Curtis DJ, Kirby MR, et al. Hmgb3: an HMG-box family member expressed in primitive hematopoietic cells that inhibits myeloid and B-cell differentiation. Blood. 2003;102:1298–306.

    Article  CAS  PubMed  Google Scholar 

  12. Rouhiainen A, Zhao X, Vanttola P, et al. HMGB4 is expressed by neuronal cells and affects the expression of genes involved in neural differentiation. Sci Rep. 2016;6:32960.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bianchi ME, Agresti A. HMG proteins: dynamic players in gene regulation and differentiation. Curr Opin Genet Dev. 2005;15:496–506.

    Article  CAS  PubMed  Google Scholar 

  14. Stros M, Launholt D, Grasser KD. The HMG-box: a versatile protein domain occurring in a wide variety of DNA-binding proteins. Cell Mol Life Sci. 2007;64:2590–606.

    Article  CAS  PubMed  Google Scholar 

  15. Pil PM, Lippard SJ. Specific binding of chromosomal protein HMG1 to DNA damaged by the anticancer drug cisplatin. Science. 1992;256:234–7.

    Article  CAS  PubMed  Google Scholar 

  16. Paull TT, Haykinson MJ, Johnson RC. The nonspecific DNA-binding and -bending proteins HMG1 and HMG2 promote the assembly of complex nucleoprotein structures. Genes Dev. 1993;7:1521–34.

    Article  CAS  PubMed  Google Scholar 

  17. Agresti A, Bianchi ME. HMGB proteins and gene expression. Curr Opin Genet Dev. 2003;13:170–8.

    Article  CAS  PubMed  Google Scholar 

  18. Boonyaratanakornkit V, Melvin V, Prendergast P, et al. High-mobility group chromatin proteins 1 and 2 functionally interact with steroid hormone receptors to enhance their DNA binding in vitro and transcriptional activity in mammalian cells. Mol Cell Biol. 1998;18:4471–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Aidinis V, Bonaldi T, Beltrame M, Santagata S, Bianchi ME, Spanopoulou E. The RAG1 homeodomain recruits HMG1 and HMG2 to facilitate recombination signal sequence binding and to enhance the intrinsic DNA-bending activity of RAG1-RAG2. Mol Cell Biol. 1999;19:6532–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Calogero S, Grassi F, Aguzzi A, et al. The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice. Nat Genet. 1999;22:276–80.

    Article  CAS  PubMed  Google Scholar 

  21. Nemeth MJ, Cline AP, Anderson SM, Garrett-Beal LJ, Bodine DM. Hmgb3 deficiency deregulates proliferation and differentiation of common lymphoid and myeloid progenitors. Blood. 2005;105:627–34.

    Article  CAS  PubMed  Google Scholar 

  22. Taniguchi N, Yoshida K, Ito T, et al. Stage-specific secretion of HMGB1 in cartilage regulates endochondral ossification. Mol Cell Biol. 2007;27:5650–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999;285:248–51.

    Article  CAS  PubMed  Google Scholar 

  24. Antoine DJ, Harris HE, Andersson U, Tracey KJ, Bianchi ME. A systematic nomenclature for the redox states of high mobility group box (HMGB) proteins. Mol Med. 2014;20:135–7.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Venereau E, Ceriotti C, Bianchi ME. DAMPs from cell death to new life. Front Immunol. 2015;6:422.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Parkkinen J, Raulo E, Merenmies J, et al. Amphoterin, the 30-kDa protein in a family of HMG1-type polypeptides. Enhanced expression in transformed cells, leading edge localization, and interactions with plasminogen activation. J Biol Chem. 1993;268:19726–38.

    CAS  PubMed  Google Scholar 

  27. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol. 2007;81:1–5.

    Article  CAS  PubMed  Google Scholar 

  28. Magna M, Pisetsky DS. The role of HMGB1 in the pathogenesis of inflammatory and autoimmune diseases. Mol Med. 2014;20:138–46.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Heinola T, de Grauw JC, Virkki L, et al. Bovine chronic osteoarthritis causes minimal change in synovial fluid. J Comp Pathol. 2013;148:335–44.

    Article  CAS  PubMed  Google Scholar 

  30. Li ZC, Cheng GQ, Hu KZ, et al. Correlation of synovial fluid HMGB-1 levels with radiographic severity of knee osteoarthritis. Clin Invest Med. 2011;34:E298.

    Article  CAS  PubMed  Google Scholar 

  31. Schierbeck H, Pullerits R, Pruunsild C, et al. HMGB1 levels are increased in patients with juvenile idiopathic arthritis, correlate with early onset of disease, and are independent of disease duration. J Rheumatol. 2013;40:1604–13.

    Article  CAS  PubMed  Google Scholar 

  32. Rosenberg AM, Cordeiro DM. Relationship between sex and antibodies to high mobility group proteins 1 and 2 in juvenile idiopathic arthritis. J Rheumatol. 2000;27:2489–93.

    CAS  PubMed  Google Scholar 

  33. Lundback P, Stridh P, Klevenvall L, et al. Characterization of the inflammatory properties of actively released HMGB1 in juvenile idiopathic arthritis. Antioxid Redox Signal. 2016;24:605–19.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Hamada T, Torikai M, Kuwazuru A, et al. Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis. Arthritis Rheum. 2008;58:2675–85.

    Article  PubMed  Google Scholar 

  35. Oestreicher JL, Walters IB, Kikuchi T, et al. Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling. Pharmacogenomics J. 2001;1:272–87.

    Article  CAS  PubMed  Google Scholar 

  36. Oktayoglu P, Em S, Tahtasiz M, et al. Elevated serum levels of high mobility group box protein 1 (HMGB1) in patients with ankylosing spondylitis and its association with disease activity and quality of life. Rheumatol Int. 2013;33:1327–31.

    Article  CAS  PubMed  Google Scholar 

  37. Pusterla T, de Marchis F, Palumbo R, Bianchi ME. High mobility group B2 is secreted by myeloid cells and has mitogenic and chemoattractant activities similar to high mobility group B1. Autoimmunity. 2009;42:308–10.

    Article  CAS  PubMed  Google Scholar 

  38. Feldmann M, Maini RN. Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Annu Rev Immunol. 2001;19:163–96.

    Article  CAS  PubMed  Google Scholar 

  39. Kim EY, Moudgil KD. Immunomodulation of autoimmune arthritis by pro-inflammatory cytokines. Cytokine. 2017;98:87–96. doi:10.1016/j.cyto.2017.04.012.

    Article  CAS  PubMed  Google Scholar 

  40. Taniguchi N, Kawahara K, Yone K, et al. High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum. 2003;48:971–81.

    Article  CAS  PubMed  Google Scholar 

  41. Kokkola R, Sundberg E, Ulfgren AK, et al. High mobility group box chromosomal protein 1: a novel proinflammatory mediator in synovitis. Arthritis Rheum. 2002;46:2598–603.

    Article  CAS  PubMed  Google Scholar 

  42. Dinarello CA, Cannon JG, Wolff SM, et al. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med. 1986;163:1433–50.

    Article  CAS  PubMed  Google Scholar 

  43. Brennan FM, Chantry D, Jackson A, Maini R, Feldmann M. Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet. 1989;2:244–7.

    Article  CAS  PubMed  Google Scholar 

  44. Wang H, Yang H, Czura CJ, Sama AE, Tracey KJ. HMGB1 as a late mediator of lethal systemic inflammation. Am J Respir Crit Care Med. 2001;164:1768–73.

    Article  CAS  PubMed  Google Scholar 

  45. Yang H, Wang H, Tracey KJ. HMG-1 rediscovered as a cytokine. Shock. 2001;15:247–53.

    Article  CAS  PubMed  Google Scholar 

  46. Muller S, Scaffidi P, Degryse B, et al. New EMBO members’ review: the double life of HMGB1 chromatin protein: architectural factor and extracellular signal. EMBO J. 2001;20:4337–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Prasad S, Thakur MK. Effects of spermine and sodium butyrate on the in vitro phosphorylation of HMG non-histone proteins of the liver of young and old rats. Arch Gerontol Geriatr. 1990;10:231–8.

    Article  CAS  PubMed  Google Scholar 

  48. Thakur MK, Prasad S. ADP-ribosylation of HMG proteins and its modulation by different effectors in the liver of aging rats. Mech Ageing Dev. 1990;53:91–100.

    Article  CAS  PubMed  Google Scholar 

  49. Prasad S, Thakur MK. Differential methylation of HMG proteins by dexamethasone in the liver of aging rats. Aging (Milano). 1991;3:333–5.

    CAS  PubMed  Google Scholar 

  50. Ly DH, Lockhart DJ, Lerner RA, Schultz PG. Mitotic misregulation and human aging. Science. 2000;287:2486–92.

    Article  CAS  PubMed  Google Scholar 

  51. Aird KM, Iwasaki O, Kossenkov AV, et al. HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci. J Cell Biol. 2016;215:325–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Hunziker EB, Quinn TM, Hauselmann HJ. Quantitative structural organization of normal adult human articular cartilage. Osteoarthr Cartil. 2002;10:564–72.

    Article  CAS  PubMed  Google Scholar 

  53. Meachim G, Collins DH. Cell counts of normal and osteoarthritic articular cartilage in relation to the uptake of sulphate (35SO4) in vitro. Ann Rheum Dis. 1962;21:45–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Goldring MB. The role of the chondrocyte in osteoarthritis. Arthritis Rheum. 2000;43:1916–26.

    Article  CAS  PubMed  Google Scholar 

  55. Kuhn K, D’Lima DD, Hashimoto S, Lotz M. Cell death in cartilage. Osteoarthr Cartil. 2004;12:1–16.

    Article  CAS  PubMed  Google Scholar 

  56. Abramson SB. Inflammation in osteoarthritis. J Rheumatol Suppl. 2004;70:70–6.

    CAS  PubMed  Google Scholar 

  57. Hiraoka K, Grogan S, Olee T, Lotz M. Mesenchymal progenitor cells in adult human articular cartilage. Biorheology. 2006;43:447–54.

    PubMed  Google Scholar 

  58. Alsalameh S, Amin R, Gemba T, Lotz M. Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage. Arthritis Rheum. 2004;50:1522–32.

    Article  PubMed  Google Scholar 

  59. Dowthwaite GP, Bishop JC, Redman SN, et al. The surface of articular cartilage contains a progenitor cell population. J Cell Sci. 2004;117:889–97.

    Article  CAS  PubMed  Google Scholar 

  60. Taniguchi N, Carames B, Ronfani L, et al. Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis. Proc Natl Acad Sci USA. 2009;106:1181–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Amin AR, Islam AB. Genomic analysis and differential expression of HMG and S100A family in human arthritis: upregulated expression of chemokines, IL-8 and nitric oxide by HMGB1. DNA Cell Biol. 2014;33:550–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Flannery CR, Hughes CE, Schumacher BL, et al. Articular cartilage superficial zone protein (SZP) is homologous to megakaryocyte stimulating factor precursor and Is a multifunctional proteoglycan with potential growth-promoting, cytoprotective, and lubricating properties in cartilage metabolism. Biochem Biophys Res Commun. 1999;254:535–41.

    Article  CAS  PubMed  Google Scholar 

  63. Rhee DK, Marcelino J, Baker M, et al. The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth. J Clin Investig. 2005;115:622–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Qi ML, Tagawa K, Enokido Y, et al. Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases. Nat Cell Biol. 2007;9:402–14.

    Article  CAS  PubMed  Google Scholar 

  65. Brezniceanu ML, Volp K, Bosser S, et al. HMGB1 inhibits cell death in yeast and mammalian cells and is abundantly expressed in human breast carcinoma. Faseb J. 2003;17:1295–7.

    CAS  PubMed  Google Scholar 

  66. Glasson SS. In vivo osteoarthritis target validation utilizing genetically-modified mice. Curr Drug Targets. 2007;8:367–76.

    Article  CAS  PubMed  Google Scholar 

  67. Poole AR, Guilak F, Abramson S. Etiopathogenesis of osteoarthritis. In: Moskowitz R, editor. Osteoarthritis. Philadelphia: Wolters Kluwer; 2007.

    Google Scholar 

  68. Johnson ML, Kamel MA. The Wnt signaling pathway and bone metabolism. Curr Opin Rheumatol. 2007;19:376–82.

    Article  CAS  PubMed  Google Scholar 

  69. Goldring SR, Goldring MB. Eating bone or adding it: the Wnt pathway decides. Nat Med. 2007;13:133–4.

    Article  CAS  PubMed  Google Scholar 

  70. Nusse R, Clevers H. Wnt/beta-catenin signaling, disease, and emerging therapeutic modalities. Cell. 2017;169:985–99.

    Article  CAS  PubMed  Google Scholar 

  71. Day TF, Guo X, Garrett-Beal L, Yang Y. Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell. 2005;8:739–50.

    Article  CAS  PubMed  Google Scholar 

  72. Koyama E, Shibukawa Y, Nagayama M, et al. A distinct cohort of progenitor cells participates in synovial joint and articular cartilage formation during mouse limb skeletogenesis. Dev Biol. 2008;316:62–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Loughlin J, Dowling B, Chapman K, et al. Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proc Natl Acad Sci USA. 2004;101:9757–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Tamamura Y, Otani T, Kanatani N, et al. Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification. J Biol Chem. 2005;280:19185–95.

    Article  CAS  PubMed  Google Scholar 

  75. Zhu M, Chen M, Zuscik M, et al. Inhibition of beta-catenin signaling in articular chondrocytes results in articular cartilage destruction. Arthritis Rheum. 2008;58:2053–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Taniguchi N, Carames B, Kawakami Y, Amendt BA, Komiya S, Lotz M. Chromatin protein HMGB2 regulates articular cartilage surface maintenance via beta-catenin pathway. Proc Natl Acad Sci USA. 2009;106:16817–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Robinson JA, Chatterjee-Kishore M, Yaworsky PJ, et al. Wnt/beta-catenin signaling is a normal physiological response to mechanical loading in bone. J Biol Chem. 2006;281:31720–8.

    Article  CAS  PubMed  Google Scholar 

  78. Akiyama H, Lyons JP, Mori-Akiyama Y, et al. Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev. 2004;18:1072–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Husa M, Liu-Bryan R, Terkeltaub R. Shifting HIFs in osteoarthritis. Nat Med. 2010;16:641–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kamekura S, Kawasaki Y, Hoshi K, et al. Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability. Arthritis Rheum. 2006;54:2462–70.

    Article  CAS  PubMed  Google Scholar 

  81. Inada M, Yasui T, Nomura S, et al. Maturational disturbance of chondrocytes in Cbfa1-deficient mice. Dev Dyn. 1999;214:279–90.

    Article  CAS  PubMed  Google Scholar 

  82. Kim IS, Otto F, Zabel B, Mundlos S. Regulation of chondrocyte differentiation by Cbfa1. Mech Dev. 1999;80:159–70.

    Article  CAS  PubMed  Google Scholar 

  83. Ueta C, Iwamoto M, Kanatani N, et al. Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes. J Cell Biol. 2001;153:87–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Stricker S, Fundele R, Vortkamp A, Mundlos S. Role of Runx genes in chondrocyte differentiation. Dev Biol. 2002;245:95–108.

    Article  CAS  PubMed  Google Scholar 

  85. Taniguchi N, Carames B, Hsu E, Cherqui S, Kawakami Y, Lotz M. Expression patterns and function of chromatin protein HMGB2 during mesenchymal stem cell differentiation. J Biol Chem. 2011;286:41489–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Dong YF, Soung do Y, Schwarz EM, O’Keefe RJ, Drissi H. Wnt induction of chondrocyte hypertrophy through the Runx2 transcription factor. J Cell Physiol. 2006;208:77–86.

    Article  CAS  PubMed  Google Scholar 

  87. Hartmann C, Tabin CJ. Dual roles of Wnt signaling during chondrogenesis in the chicken limb. Development. 2000;127:3141–59.

    CAS  PubMed  Google Scholar 

  88. Daumer KM, Tufan AC, Tuan RS. Long-term in vitro analysis of limb cartilage development: involvement of Wnt signaling. J Cell Biochem. 2004;93:526–41.

    Article  CAS  PubMed  Google Scholar 

  89. Drissi H, Luc Q, Shakoori R, et al. Transcriptional autoregulation of the bone related CBFA1/RUNX2 gene. J Cell Physiol. 2000;184:341–50.

    Article  CAS  PubMed  Google Scholar 

  90. Drissi H, Pouliot A, Stein JL, van Wijnen AJ, Stein GS, Lian JB. Identification of novel protein/DNA interactions within the promoter of the bone-related transcription factor Runx2/Cbfa1. J Cell Biochem. 2002;86:403–12.

    Article  CAS  PubMed  Google Scholar 

  91. Lengner CJ, Hassan MQ, Serra RW, et al. Nkx3.2-mediated repression of Runx2 promotes chondrogenic differentiation. J Biol Chem. 2005;280:15872–9.

    Article  CAS  PubMed  Google Scholar 

  92. Tamiya H, Ikeda T, Jeong JH, et al. Analysis of the Runx2 promoter in osseous and non-osseous cells and identification of HIF2A as a potent transcription activator. Gene. 2008;416:53–60.

    Article  CAS  PubMed  Google Scholar 

  93. Drissi H, Pouliot A, Koolloos C, et al. 1,25-(OH)2-vitamin D3 suppresses the bone-related Runx2/Cbfa1 gene promoter. Exp Cell Res. 2002;274:323–33.

    Article  CAS  PubMed  Google Scholar 

  94. Kahler RA, Westendorf JJ. Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter. J Biol Chem. 2003;278:11937–44.

    Article  CAS  PubMed  Google Scholar 

  95. Hasegawa A, Yonezawa T, Taniguchi N, et al. Role of fibulin 3 in aging-related joint changes and osteoarthritis pathogenesis in human and mouse knee cartilage. Arthritis Rheumatol. 2017;69:576–85.

    Article  CAS  PubMed  Google Scholar 

  96. Zhang Y, Marmorstein LY. Focus on molecules: fibulin-3 (EFEMP1). Exp Eye Res. 2010;90:374–5.

    Article  CAS  PubMed  Google Scholar 

  97. McLaughlin PJ, Bakall B, Choi J, et al. Lack of fibulin-3 causes early aging and herniation, but not macular degeneration in mice. Hum Mol Genet. 2007;16:3059–70.

    Article  CAS  PubMed  Google Scholar 

  98. Ehlermann J, Weber S, Pfisterer P, Schorle H. Cloning, expression and characterization of the murine Efemp1, a gene mutated in Doyne–Honeycomb retinal dystrophy. Gene Expr Patterns. 2003;3:441–7.

    Article  CAS  PubMed  Google Scholar 

  99. Henrotin Y, Gharbi M, Mazzucchelli G, Dubuc JE, De Pauw E, Deberg M. Fibulin 3 peptides Fib3-1 and Fib3-2 are potential biomarkers of osteoarthritis. Arthritis Rheum. 2012;64:2260–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful for the support from Hiroshi Asahara (Tokyo Medical and Dental University, Japan), Marco E Bianchi (San Raffaele University, Italy), Diana Brinson, Lilo Creighton and Jean Valbracht (The Scripps Research Institute, USA). This work was funded by grants from MEXT KAKENHI (Grant number 15K10484 to NT) and the NIH (Grant numbers AR064195 to YK and AG007996 to ML).

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan

    Noboru Taniguchi

  2. Department of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan

    Noboru Taniguchi

  3. Department of Genetics, Cell Biology and Development, and Stem Cell Institute, University of Minnesota, 321 Church St. SE, 6-160 Jackson Hall, Minneapolis, MN, 55455, USA

    Yasuhiko Kawakami

  4. Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, 890-8544, Japan

    Ikuro Maruyama

  5. Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Road, MEM 161, La Jolla, CA, 92037, USA

    Martin Lotz

Authors
  1. Noboru Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuhiko Kawakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ikuro Maruyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin Lotz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Noboru Taniguchi.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Taniguchi, N., Kawakami, Y., Maruyama, I. et al. HMGB proteins and arthritis. Human Cell 31, 1–9 (2018). https://doi.org/10.1007/s13577-017-0182-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-017-0182-x

Keywords

Search

Navigation