Paricalcitol inhibits the Wnt/beta-catenin signaling pathway and ameliorates experimentally induced arthritis

Paricalcitol inhibits the Wnt/beta-catenin signaling pathway and ameliorates experimentally induced arthritis

Background/aim: The Wnt/β-catenin pathway has important biological activities, including the differentiation of cells and jointformations. The aim of our study was to determine the effect of paricalcitol on experimentally induced arthritis.Materials and methods: Type II collagen combined with Freund’s adjuvant was applied to induce arthritis in Wistar albino female rats.Paricalcitol (0.3 µg/kg daily) was subcutaneously injected starting 1 day after collagen applications (prophylactic group) or 1 day afterthe onset of arthritis (therapeutic group), until day 29.Results: The 29th day arthritis scores were lower compared to the 13th day scores in the paricalcitol groups (P < 0.05), while they werehigher in the arthritis group (P < 0.05). Marked cartilage-bone destruction and extensive perisynovial inflammation were detected inthe arthritis group. Decreased cartilage-bone destruction and perisynovial inflammation in the paws were observed in the paricalcitolgroups. The tissue mRNA levels of DKK1, Wnt5a, and axin-2 were higher in the arthritis group than in the control group. In theparicalcitol groups, mRNA expressions were lower than in the arthritis group.Conclusion: The present study shows that the Wnt/β-catenin signaling pathway is active in arthritis. Moreover, paricalcitol amelioratesarthritis via inhibiting the Wnt/β-catenin pathway. Paricalcitol and the Wnt/β-catenin pathway are candidates for research in humanrheumatoid arthritis.

___

  • Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet 2010; 376: 1094-1108.
  • Nurmohamed MT, Dijkmans BA. Efficacy, tolerability and cost effectiveness of disease-modifying antirheumatic drugs and biologic agents in rheumatoid arthritis. Drugs 2005; 65: 661- 694.
  • Salliot C, Finckh A, Katchamart W, Lu Y, Sun Y, Bombardier C, Keystone E. Indirect comparisons of the efficacy of biological antirheumatic agents in rheumatoid arthritis in patients with an inadequate response to conventional disease-modifying antirheumatic drugs or to an anti-tumour necrosis factor agent: a meta-analysis. Ann Rheum Dis 2011; 70: 266-271.
  • Mavers M, Ruderman EM, Perlman H. Intracellular signal pathways: potential for therapies. Curr Rheumatol Rep 2009; 11: 378-385.
  • Rabelo Fde S, da Mota LM, Lima RA, Lima FA, Barra GB, de Carvalho JF, Amato AA. The Wnt signaling pathway and rheumatoid arthritis. Autoimmun Rev 2010; 9: 207-210.
  • Shaw AT, Gravallese EM. Mediators of inflammation and bone remodeling in rheumatic disease. Semin Cell Dev Biol 2016; 49: 2-10.
  • Van Amerongen R, Nusse R. Towards an integrated view of Wnt signaling in development. Development 2009; 136: 3205-3214.
  • Sen M, Lauterbach K, El-Gabalawy H, Firestein GS, Corr M, Carson DA. Expression and function of wingless and frizzled homologs in rheumatoid arthritis. P Natl Acad Sci USA 2000; 97: 2791-2796.
  • Nakamura Y, Nawata M, Wakitani S. Expression profiles and functional analyses of Wnt-related genes in human joint disorders. Am J Pathol 2005; 167: 97-105.
  • Imai K, Morikawa M, D’Armiento J, Matsumoto H, Komiya K, Okada Y. Differential expression of WNTs and FRPs in thes ynovium of rheumatoid arthritis and osteoarthritis. Biochem Biophys Res Commun 2006; 345: 1615-1620.
  • Sen M, Reifert J, Lauterbach K, Wolf V, Rubin JS, Corr M, Carson DA. Regulation of fibronectin and metalloproteinase expression by Wnt signaling in rheumatoid arthritis synoviocytes. Arthritis Rheum 2002; 46: 2867-2877.
  • Notani D, Gottimukkala KP, Jayani RS, Limaye AS, Damle MV, Mehta S, Purbey PK, Joseph J, Galande S. Global regulator SATB1 recruits beta-catenin and regulates T(H)2 differentiation in Wnt-dependent manner. PLoS Biol 2010; 8: e1000296.
  • Yu Q, Sharma A, Oh SY, Moon HG, Hossain MZ, Salay TM, Leeds KE, Du H, Wu B, Waterman ML et al. T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-gamma. Nat Immunol 2009; 10: 992-999.
  • Ding Y, Shen S, Lino AC, Curotto de Lafaille MA, Lafaille JJ. Beta-catenin stabilization extends regulatory T cell survival and induces anergy in nonregulatory T cells. Nat Med 2008; 14: 162- 169.
  • Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D, Korb A, Smolen J, Hoffmann M, Scheinecker C et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007; 13: 156-163.
  • Martínez-Moreno JM, Muñoz-Castañeda JR, Herencia C, Oca AM, Estepa JC, Canalejo R, Rodríguez-Ortiz ME, PerezMartinez P, Aguilera-Tejero E, Canalejo A et al. In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/β-catenin activation. Am J Physiol Renal Physiol 2012; 303: F1136-1144.
  • He W, Kang YS, Dai C, Liu Y. Blockade of Wnt/β-catenin signaling by paricalcitol ameliorates proteinuria and kidney injury. J Am Soc Nephrol 2011; 22: 90-103.
  • Tan X, Wen X, Liu Y. Paricalcitol inhibits renal inflammation by promoting vitamin D receptor-mediated sequestration of NF-kappaB signaling. J Am Soc Nephrol 2008; 19: 1741-1752.
  • Navarro-González JF, Donate-Correa J, Méndez ML, de Fuentes MM, García-Pérez J, Mora-Fernández C. Anti-inflammatory profile of paricalcitol in hemodialysis patients: a prospective, open-label, pilot study. J Clin Pharmacol 2013; 53: 421-426.
  • Izquierdo MJ, Cavia M, Muñiz P, de Francisco AL, Arias M, Santos J, Abaigar P. Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients. BMC Nephrol 2012; 13: 159.
  • Trentham DE, Townes AS, Kang AH. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med 1977; 146: 857-868.
  • Duffy MM, McNicholas BA, Monaghan DA, Hanley SA, McMahon JM, Pindjakova J, Alagesan S, Fearnhead HO, Griffin MD. Mesenchymal stem cells and a vitamin D receptor agonist additively suppress T helper 17 cells and the related inflammatory response in the kidney. Am J Physiol Renal Physiol 2014; 307: F1412-F1426.
  • Barsante MM, Roffê E, Yokoro CM, Tafuri WL, Souza DG, Pinho V, Castro MS, Teixeira MM. Anti-inflammatory and analgesic effects of atorvastatin in a rat model of adjuvantinduced arthritis. Eur J Pharmacol 2005; 516: 282-289.
  • Buran İ, Etem EÖ, Tektemur A, Elyas H. Treatment with TREK1 and TRPC3/6 ion channel inhibitors upregulates microRNA expression in a mouse model of chronic mild stress. Neurosci Lett. 2017; 656: 51-57.
  • Semerano L, Minichiello E, Bessis N, Boissier MC. Novel immunotherapeutic avenues for rheumatoid arthritis. Trends Mol Med 2016; 22: 214-229
  • Maeda K, Takahashi N, Kobayashi Y. Roles of Wnt signals in bone resorption during physiological and pathological states. J Mol Med (Berl) 2013; 91: 15-23.
  • Xiao CY, Pan YF, Guo XH, Wu YQ, Gu JR, Cai DZ. Expression of β-catenin in rheumatoid arthritis fibroblast-like synoviocytes. Scand J Rheumatol 2011; 40: 26-33.
  • Miao CG, Yang YY, He X, Li XF, Huang C, Huang Y, Zhang L, Lv XW, Jin Y, Li J. Wnt signaling pathway in rheumatoid arthritis, with special emphasis on the different roles in synovial inflammation and bone remodeling. Cell Signal 2013; 25: 2069-2078.
  • Rauner M, Stein N, Winzer M, Goettsch C, Zwerina J, Schett G, Distler JH, Albers J, Schulze J, Schinke T et al. WNT5A is induced by inflammatory mediators in bone marrow stromal cells and regulates cytokine and chemokine production. J Bone Miner Res 2012; 27: 575-585.
  • Baum R, Gravallese EM. Bone as a target organ in rheumatic disease: impact on osteoclasts and osteoblasts. Clinic Rev Allerg Immunol Clin Rev Allergy Immunol 2016; 51: 1-15.
  • Kim TH, Ji JD. Paricalcitol, a synthetic vitamin D analog: a candidate for combination therapy with biological agents in rheumatoid arthritis. Med Hypotheses 2010; 75: 634-635.
  • Kobayashi Y, Uehara S, Udagawa N, Takahashi N. Regulation of bone metabolism by Wnt signals. J Biochem 2016; 159: 387- 392.
  • Wang SY, Liu YY, Ye H, Guo JP, Li R, Liu X, Li ZG. Circulating Dickkopf-1 is correlated with bone erosion and inflammation in rheumatoid arthritis. J Rheumatol 2011; 38: 821-827.
  • Leung JY, Kolligs FT, Wu R, Zhai Y, Kuick R, Hanash S, Cho KR, Fearon ER. Activation of AXIN2 expression by betacatenin-T cell factor. A feedback repressor pathway regulating Wnt signaling. J Biol Chem 2002; 277: 21657-21665.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Effects of computer-assisted cognitive rehabilitation in benign multiple sclerosis

Recai TÜRKOĞLU, Erdem TÜZÜN, Erdil ARSOY

Özge AKSEL KILIÇARSLAN, Esra ATAMAN, Semra GÜRSOY, Filiz HAZAN, Cemre RANDA, Tufan ÇANKAYA, Derya ERÇAL, Ayfer ÜLGENALP, Özlem GİRAY BOZKAYA

Ahmet BEŞİR, Ersagun TUĞCUGİL

The use of rapid antigen testing and matrix-assisted laser desorption/ionization-time of flight mass spectrometry in the diagnosis of group A beta-hemolytic streptococci in throat swab samples

Ayşe BARIŞ, Banu BAYRAKTAR, Elif AKTAŞ, Rıdvan DENİZ

The role of melatonin in preventing ovarian tissue damage in rats exposed to magnetic fields

Uğurkan ERKAYIRAN, Deniz KARCAALTINCABA, Muzaffer ÇAYDERE, Damla KAYAALP, Zahide KÜÇÜK

Gizem GÜRSOY, Kemal TUTKAVUL, Yılmaz ÇETİNKAYA, Hülya TİRELİ

Ramazan DERTLİ, Muharrem KESKİN, Murat BIYIK, Hüseyin ATASEVEN, Hakkı POLAT, Ali DEMİR, Pembe OLTULU, Salim NEŞELOĞLU, Özcan EREL, Mehmet ASIL

Ultrasonographic and clinical evaluation of additional contribution of kinesiotaping to tendon and nerve gliding exercises in the treatment of carpal tunnel syndrome

Pınar YILDIRIM, Ebru ŞAHİN, Ramazan KIZIL, Selmin GÜLBAHAR, Banu DİLEK

Invasive nontyphoidal Salmonella disease in southern India: a 5-year experience from a tertiary care hospital

Sudipta PATRA, Yasha MUKIM, Muralidhar VARMA, Chiranjay MUKHOPADHYAY, Vandana KALWAJE ESHWARA

Is NREM-predominant obstructive sleep apnea syndrome a different clinical entity?

Mehmet İlker YÖN, Oğuz KÖKTÜRK