Login Register Cart 0
Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Effect of Estradiol on Chondrocytes in the Active Stage of Collagenase- Induced Osteoarthritis

Author(s): Petya Ganova, Lyudmila Belenska-Todorova and Nina Ivanovska*

Volume 19, Issue 1, 2023

Published on: 11 March, 2022

Article ID: e180122200319 Pages: 8

DOI: 10.2174/1573407218666220118094935

Price: $65

conference banner
Abstract

Aim: The aim of the present study is to examine the effect of estradiol on chondrocyte inflammatory potential and apoptosis in a mouse model of osteoarthritis (OA).

Background: OA is a degenerative joint disease related to articular cartilage disintegration, together with substantial changes in the subchondral bone. Estradiol (ED) is considered to be an important player in maintaining bone homeostasis. Increasing evidence support the association between the severity of cartilage erosion and chondrocyte death.

Objective: It is of great importance to elucidate the role of chondrocytes in the development of OA in relation to estrogen levels.

Methods: The present work was conducted on a model of collagenase-induced osteoarthritis (CIOA) in ICR (CD-2) mice. The cytokine and MMP-3 concentrations were assayed by ELISA, and apoptosis of chondrocytes was determined by flow cytometry.

Results: ED decreased the number of cultured TGF-β1 positive chondrocytes, reduced the percentage of double-positive CD220+/TNF-α+ chondrocytes. ED reduced the rate of apoptosis and MMP- 13 production of stimulated arthritic chondrocytes, and inhibited the release of inflammatory IL-6 and IL-8 cytokines in vitro.

Conclusion: Our results show that ED affects chondrocyte functions as a part of its anti-arthritic mechanism of action and it might be a perspective drug for healing OA.

Keywords: Estradiol, chondrocytes, collagenase-induced osteoarthritis (CIOA), IL-6, IL-8, MMP-13.

Graphical Abstract

[1]
Cross, M.; Smith, E.; Hoy, D.; Nolte, S.; Ackerman, I.; Fransen, M.; Bridgett, L.; Williams, S.; Guillemin, F.; Hill, C.L.; Laslett, L.L.; Jones, G.; Cicuttini, F.; Osborne, R.; Vos, T.; Buchbinder, R.; Woolf, A.; March, L. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann. Rheum. Dis., 2014, 73(7), 1323-1330.
[http://dx.doi.org/10.1136/annrheumdis-2013-204763] [PMID: 24553908]
[2]
Glyn-Jones, S.; Palmer, A.J.; Agricola, R.; Price, A.J.; Vincent, T.L.; Weinans, H.; Carr, A.J. Osteoarthritis. Lancet, 2015, 386(9991), 376-387.
[http://dx.doi.org/10.1016/S0140-6736(14)60802-3] [PMID: 25748615]
[3]
Blanco, F.J.; Guitian, R.; Vázquez-Martul, E.; de Toro, F.J.; Galdo, F. Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology. Arthritis Rheum., 1998, 41(2), 284-289.
[http://dx.doi.org/10.1002/1529-0131(199802)41:2<284::AID-ART12>3.0.CO;2-T] [PMID: 9485086]
[4]
Thomas, C.M.; Fuller, C.J.; Whittles, C.E.; Sharif, M. Chondrocyte death by apoptosis is associated with cartilage matrix degradation. Osteoarthritis Cartilage, 2007, 15(1), 27-34.
[http://dx.doi.org/10.1016/j.joca.2006.06.012] [PMID: 16859932]
[5]
Kim, H.A.; Blanco, F.J. Cell death and apoptosis in osteoarthritic cartilage. Curr. Drug Targets, 2007, 8(2), 333-345.
[http://dx.doi.org/10.2174/138945007779940025] [PMID: 17305511]
[6]
Aigner, T.; Hemmel, M.; Neureiter, D.; Gebhard, P.M.; Zeiler, G.; Kirchner, T.; McKenna, L. Apoptotic cell death is not a widespread phenomenon in normal aging and osteoarthritis human articular knee cartilage: a study of proliferation, programmed cell death (apoptosis), and viability of chondrocytes in normal and osteoarthritic human knee cartilage. Arthritis Rheum., 2001, 44(6), 1304-1312.
[http://dx.doi.org/10.1002/1529-0131(200106)44:6<1304::AID-ART222>3.0.CO;2-T] [PMID: 11407689]
[7]
Hwang, H.S.; Kim, H.A. Chondrocyte apoptosis in the pathogenesis of osteoarthritis. Int. J. Mol. Sci., 2015, 16(11), 26035-26054.
[http://dx.doi.org/10.3390/ijms161125943] [PMID: 26528972]
[8]
Schuerwegh, A.J.; Dombrecht, E.J.; Stevens, W.J.; Van Offel, J.F.; Bridts, C.H.; De Clerck, L.S. Influence of pro-inflammatory (IL-1 alpha, IL-6, TNF-alpha, IFN-gamma) and anti-inflammatory (IL-4) cytokines on chondrocyte function. Osteoarthritis Cartilage, 2003, 11(9), 681-687.
[http://dx.doi.org/10.1016/S1063-4584(03)00156-0] [PMID: 12954239]
[9]
Pettersen, I.; Figenschau, Y.; Olsen, E.; Bakkelund, W.; Smedsröd, B.; Sveinbjörnsson, B. Tumor necrosis factor-related apoptosis-inducing ligand induces apoptosis in human articular chondrocytes in vitro. Biochem. Biophys. Res. Commun., 2002, 296(3), 671-676.
[http://dx.doi.org/10.1016/S0006-291X(02)00916-6] [PMID: 12176034]
[10]
Lee, S.W.; Lee, H.J.; Chung, W.T.; Choi, S.M.; Rhyu, S.H.; Kim, D.K.; Kim, K.T.; Kim, J.Y.; Kim, J.M.; Yoo, Y.H. TRAIL induces apoptosis of chondrocytes and influences the pathogenesis of experimentally induced rat osteoarthritis. Arthritis Rheum., 2004, 50(2), 534-542.
[http://dx.doi.org/10.1002/art.20052] [PMID: 14872496]
[11]
Ström, J.O.; Theodorsson, A.; Ingberg, E.; Isaksson, I.M.; Theodorsson, E. Ovariectomy and 17β-estradiol replacement in rats and mice: A visual demonstration. J. Vis. Exp., 2012, (64), e4013.
[PMID: 22710371]
[12]
Ingberg, E.; Theodorsson, A.; Theodorsson, E.; Strom, J.O. Methods for long-term 17β-estradiol administration to mice. Gen. Comp. Endocrinol., 2012, 175(1), 188-193.
[http://dx.doi.org/10.1016/j.ygcen.2011.11.014] [PMID: 22137913]
[13]
Isaksson, I.M.; Theodorsson, A.; Theodorsson, E.; Strom, J.O. Methods for 17β-oestradiol administration to rats. Scand. J. Clin. Lab. Invest., 2011, 71(7), 583-592.
[http://dx.doi.org/10.3109/00365513.2011.596944] [PMID: 21834617]
[14]
Akkiraju, H.; Nohe, A. Role of chondrocytes in cartilage formation, progression of osteoarthritis and cartilage regeneration. J. Dev. Biol., 2015, 3(4), 177-192.
[http://dx.doi.org/10.3390/jdb3040177] [PMID: 27347486]
[15]
Archer, C.W.; Francis-West, P. The chondrocyte. Int. J. Biochem. Cell Biol., 2003, 35(4), 401-404.
[http://dx.doi.org/10.1016/S1357-2725(02)00301-1] [PMID: 12565700]
[16]
Buckwalter, J.A.; Mankin, H.J.; Grodzinsky, A.J. Articular cartilage and osteoarthritis. Instr. Course Lect., 2005, 54, 465-480.
[PMID: 15952258]
[17]
Kapoor, M.; Martel-Pelletier, J.; Lajeunesse, D.; Pelletier, J.P.; Fahmi, H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat. Rev. Rheumatol., 2011, 7(1), 33-42.
[http://dx.doi.org/10.1038/nrrheum.2010.196] [PMID: 21119608]
[18]
Falah, M.; Nierenberg, G.; Soudry, M.; Hayden, M.; Volpin, G. Treatment of articular cartilage lesions of the knee. Int. Orthop., 2010, 34(5), 621-630.
[http://dx.doi.org/10.1007/s00264-010-0959-y] [PMID: 20162416]
[19]
Fortier, L.A.; Barker, J.U.; Strauss, E.J.; McCarrel, T.M.; Cole, B.J. The role of growth factors in cartilage repair. Clin. Orthop. Relat. Res., 2011, 469(10), 2706-2715.
[http://dx.doi.org/10.1007/s11999-011-1857-3] [PMID: 21403984]
[20]
Li, G.; Jiang, X.; Liu, L.; Liu, X.; Liu, H.; Zhang, Z. Effect of estradiol on high glucose-induced osteoblast injury. Mol. Med. Rep., 2019, 20(4), 3019-3026.
[http://dx.doi.org/10.3892/mmr.2019.10552] [PMID: 31432111]
[21]
Gao, Y.; Qian, W.P.; Dark, K.; Toraldo, G.; Lin, A.S.; Guldberg, R.E.; Flavell, R.A.; Weitzmann, M.N.; Pacifici, R. Estrogen prevents bone loss through transforming growth factor beta signaling in T cells. Proc. Natl. Acad. Sci. USA, 2004, 101(47), 16618-16623.
[http://dx.doi.org/10.1073/pnas.0404888101] [PMID: 15531637]
[22]
Greenhalgh, D.G. The role of apoptosis in wound healing. Int. J. Biochem. Cell Biol., 1998, 30(9), 1019-1030.
[http://dx.doi.org/10.1016/S1357-2725(98)00058-2] [PMID: 9785465]
[23]
Musumeci, G.; Castrogiovanni, P.; Trovato, F.M.; Weinberg, A.M.; Al-Wasiyah, M.K.; Alqahtani, M.H.; Mobasheri, A. Biomarkers of chondrocyte apoptosis and autophagy in osteoarthritis. Int. J. Mol. Sci., 2015, 16(9), 20560-20575.
[http://dx.doi.org/10.3390/ijms160920560] [PMID: 26334269]
[24]
Zamli, Z.; Sharif, M. Chondrocyte apoptosis: A cause or consequence of osteoarthritis? Int. J. Rheum. Dis., 2011, 14(2), 159-166.
[http://dx.doi.org/10.1111/j.1756-185X.2011.01618.x] [PMID: 21518315]
[25]
Héraud, F.; Héraud, A.; Harmand, M.F. Apoptosis in normal and osteoarthritic human articular cartilage. Ann. Rheum. Dis., 2000, 59(12), 959-965.
[http://dx.doi.org/10.1136/ard.59.12.959] [PMID: 11087699]
[26]
Latourte, A.; Cherifi, C.; Maillet, J.; Ea, H.K.; Bouaziz, W.; Funck-Brentano, T.; Cohen-Solal, M.; Hay, E.; Richette, P. Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis. Ann. Rheum. Dis., 2017, 76(4), 748-755.
[http://dx.doi.org/10.1136/annrheumdis-2016-209757] [PMID: 27789465]
[27]
Reboul, P.; Pelletier, J.P.; Tardif, G.; Cloutier, J.M.; Martel-Pelletier, J. The new collagenase, collagenase-3, is expressed and synthesized by human chondrocytes but not by synoviocytes. A role in osteoarthritis. J. Clin. Invest., 1996, 97(9), 2011-2019.
[http://dx.doi.org/10.1172/JCI118636] [PMID: 8621789]
[28]
Yamamoto, K.; Okano, H.; Miyagawa, W.; Visse, R.; Shitomi, Y.; Santamaria, S.; Dudhia, J.; Troeberg, L.; Strickland, D.K.; Hirohata, S.; Nagase, H. MMP-13 is constitutively produced in human chondrocytes and co-endocytosed with ADAMTS-5 and TIMP-3 by the endocytic receptor LRP1. Matrix Biol., 2016, 56, 57-73.
[http://dx.doi.org/10.1016/j.matbio.2016.03.007] [PMID: 27084377]
[29]
Lindy, O.; Konttinen, Y.T.; Sorsa, T.; Ding, Y.; Santavirta, S.; Ceponis, A.; López-Otín, C. Matrix metalloproteinase 13 (collagenase 3) in human rheumatoid synovium. Arthritis Rheum., 1997, 40(8), 1391-1399.
[http://dx.doi.org/10.1002/art.1780400806] [PMID: 9259418]
[30]
Little, C.B.; Barai, A.; Burkhardt, D.; Smith, S.M.; Fosang, A.J.; Werb, Z.; Shah, M.; Thompson, E.W. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum., 2009, 60(12), 3723-3733.
[http://dx.doi.org/10.1002/art.25002] [PMID: 19950295]
[31]
Wang, W.; Wang, L.; Xu, Z.; Yin, Y.; Su, J.; Niu, X.; Cao, X. Effects of estradiol on reduction of osteoarthritis in rabbits through effect on matrix metalloproteinase proteins. Iran. J. Basic Med. Sci., 2016, 19(3), 310-315.
[PMID: 27114801]
[32]
Ganova, P.; Zhivkova, R.; Kolarov, A.; Ivanovska, N. Influence of estradiol treatment on bone marrow cell differentiation in collagenase-induced arthritis. Inflamm. Res., 2020, 69(5), 533-543.
[http://dx.doi.org/10.1007/s00011-020-01338-w] [PMID: 32200413]
[33]
Roustan, A.; Perrin, J.; Berthelot-Ricou, A.; Lopez, E.; Botta, A.; Courbiere, B. Evaluating methods of mouse euthanasia on the oocyte quality: Cervical dislocation versus isoflurane inhalation. Lab. Anim., 2012, 46(2), 167-169.
[http://dx.doi.org/10.1258/la.2012.011115] [PMID: 22511734]
[34]
Munn, D.H.; Beall, A.C.; Song, D.; Wrenn, R.W.; Throckmorton, D.C. Activation-induced apoptosis in human macrophages: developmental regulation of a novel cell death pathway by macrophage colony-stimulating factor and interferon gamma. J. Exp. Med., 1995, 181(1), 127-136.
[http://dx.doi.org/10.1084/jem.181.1.127] [PMID: 7806999]
[35]
Gyurkovska, V.; Stefanova, T.; Dimitrova, P.; Danova, S.; Tropcheva, R.; Ivanovska, N. Tyrosine kinase inhibitor tyrphostin AG490 retards chronic joint inflammation in mice. Inflammation, 2014, 37(4), 995-1005.
[http://dx.doi.org/10.1007/s10753-014-9820-6] [PMID: 24473905]
[36]
Varin, A.; Pontikoglou, C.; Labat, E.; Deschaseaux, F.; Sensebé, L. CD200R/CD200 inhibits osteoclastogenesis: New mechanism of osteoclast control by mesenchymal stem cells in human. PLoS One, 2013, 8(8), e72831.
[http://dx.doi.org/10.1371/journal.pone.0072831] [PMID: 23940819]
[37]
Mehana, E.E.; Khafaga, A.F.; El-Blehi, S.S. The role of matrix metalloproteinases in osteoarthritis pathogenesis: An updated review. Life Sci., 2019, 234, 116786.
[http://dx.doi.org/10.1016/j.lfs.2019.116786] [PMID: 31445934]
[38]
Wan, Y.; Li, W.; Liao, Z.; Yan, M.; Chen, X.; Tang, Z. Selective MMP-13 inhibitors: Promising agents for the therapy of osteoarthritis. Curr. Med. Chem., 2020, 27(22), 3753-3769.
[http://dx.doi.org/10.2174/0929867326666181217153118] [PMID: 30556497]
[39]
Goldring, M.B.; Berenbaum, F. The regulation of chondrocyte function by proinflammatory mediators: Prostaglandins and nitric oxide. Clin. Orthop. Relat. Res., 2004, (427)(Suppl.), S37-S46.
[http://dx.doi.org/10.1097/01.blo.0000144484.69656.e4] [PMID: 15480072]
[40]
Roman-Blas, J.A.; Castañeda, S.; Largo, R.; Herrero-Beaumont, G. Osteoarthritis associated with estrogen deficiency. Arthritis Res. Ther., 2009, 11(5), 241.
[http://dx.doi.org/10.1186/ar2791] [PMID: 19804619]
[41]
Travis, R.C.; Key, T.J. Oestrogen exposure and breast cancer risk. Breast Cancer Res., 2003, 5(5), 239-247.
[http://dx.doi.org/10.1186/bcr628] [PMID: 12927032]
[42]
Nie, X.; Xie, R.; Tuo, B. Effects of estrogen on the gastrointestinal tract. Dig. Dis. Sci., 2018, 63(3), 583-596.
[http://dx.doi.org/10.1007/s10620-018-4939-1] [PMID: 29387989]
[43]
Abou-Ismail, M.Y.; Citla Sridhar, D.; Nayak, L. Estrogen and thrombosis: A bench to bedside review. Thromb. Res., 2020, 192, 40-51.
[http://dx.doi.org/10.1016/j.thromres.2020.05.008] [PMID: 32450447]
[44]
Koellhoffer, E.C.; McCullough, L.D. The effects of estrogen in ischemic stroke. Transl. Stroke Res., 2013, 4(4), 390-401.
[http://dx.doi.org/10.1007/s12975-012-0230-5] [PMID: 24323337]

Rights & Permissions Print Cite
Article Metrics
4
© 2024 Bentham Science Publishers | Privacy Policy