The role of osteoprotegerin (OPG) in fibrosis: its potential as a biomarker and/or biological target for the treatment of fibrotic diseases

Habibie H., Adhyatmika A., Schaafsma D., Melgert B.N.

University of Groningen, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Groningen, Netherlands; University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, Netherlands; Hasanuddin University, Faculty of Pharmacy, Makassar, Indonesia; Gadjah Mada University, Department of Pharmaceutics, Faculty of Pharmacy, Yogyakarta, Indonesia; Science Impact, Winnipeg, Canada


Abstract

Fibrosis is defined by excessive formation and accumulation of extracellular matrix proteins, produced by myofibroblasts, that supersedes normal wound healing responses to injury and results in progressive architectural remodelling. Fibrosis is often detected in advanced disease stages when an organ is already severely damaged and can no longer function properly. Therefore, there is an urgent need for reliable and easily detectable markers to identify and monitor fibrosis onset and progression as early as possible; this will greatly facilitate the development of novel therapeutic strategies. Osteoprotegerin (OPG), a well-known regulator of bone extracellular matrix and most studied for its role in regulating bone mass, is expressed in various organs and functions as a decoy for receptor activator of nuclear factor kappa-B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Recently, OPG has been linked to fibrosis and fibrogenesis, and has been included in a panel of markers to diagnose liver fibrosis. Multiple studies now suggest that OPG may be a general biomarker suitable for detection of fibrosis and/or monitoring the impact of fibrosis treatment. This review summarizes our current understanding of the role of OPG in fibrosis and will discuss its potential as a biomarker and/or novel therapeutic target for fibrosis. © 2021 The Authors

Fibroblast; Lung; RANKL; TGFβ; TNFRSF11B; TRAIL


Journal

Pharmacology and Therapeutics

Publisher: Elsevier Inc.

Volume 228, Issue , Art No 107941, Page – , Page Count


Journal Link: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85109443921&doi=10.1016%2fj.pharmthera.2021.107941&partnerID=40&md5=e6b5665ac922be3ad151f96ffcbb18b9

doi: 10.1016/j.pharmthera.2021.107941

Issn: 01637258

Type: All Open Access, Hybrid Gold


References

Adhyatmika, A., Beljaars, L., Putri, K.S.S., Habibie, H., Boorsma, C.E., Reker-Smit, C., Melgert, B.N., Osteoprotegerin is more than a possible serum marker in liver fibrosis: A study into its function in human and murine liver (2020) Pharmaceutics, 12, p. 471; Adhyatmika, A., Putri, K.S.S., Gore, E., Mangnus, K.A., Reker-Smit, C., Schuppan, D., Melgert, B.N., Osteoprotegerin expression in liver is induced by IL-13 through TGF-β (2020) bioRxiv; Anderson, D.M., Maraskovsky, E., Billingsley, W.L., Dougall, W.C., Tometsko, M.E., Roux, E.R., Galibert, L., A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function (1997) Nature, 390, pp. 175-179; Annes, J.P., Munger, J.S., Rifkin, D.B., Making sense of latent TGFbeta activation (2003) Journal of Cell Science, 116, pp. 217-224; Ariyasu, T., Arai, C., Yoshizane, C., Kyono, F., Hanaya, T., Arai, S., Kurimoto, M., Trehalose augments osteoprotegerin production in the FHs74Int human intestinal epithelial cell line (2002) In Vitro Cellular & Developmental Biology. Animal, 38, pp. 30-34; Arnold, N.D., Pickworth, J.A., West, L.E., Dawson, S., Carvalho, J.A., Casbolt, H., Lawrie, A., A therapeutic antibody targeting osteoprotegerin attenuates severe experimental pulmonary arterial hypertension (2019) Nature Communications, 10, p. 5183; Asano, Y., Ihn, H., Yamane, K., Jinnin, M., Mimura, Y., Tamaki, K., Involvement of alphavbeta5 integrin-mediated activation of latent transforming growth factor beta1 in autocrine transforming growth factor beta signaling in systemic sclerosis fibroblasts (2005) Arthritis and Rheumatism, 52, pp. 2897-2905; Bataller, R., Brenner, D.A., Hepatic stellate cells as a target for the treatment of liver fibrosis (2001) Seminars in Liver Disease, 21, pp. 437-451; Baud’huin, M., Duplomb, L., Teletchea, S., Charrier, C., Maillasson, M., Fouassier, M., Heymann, D., Factor VIII-von Willebrand factor complex inhibits osteoclastogenesis and controls cell survival (2009) The Journal of Biological Chemistry, 284, pp. 31704-31713; Benslimane-Ahmim, Z., Heymann, D., Dizier, B., Lokajczyk, A., Brion, R., Laurendeau, I., Boisson-Vidal, C., Osteoprotegerin, a new actor in vasculogenesis, stimulates endothelial colony-forming cells properties (2011) Journal of Thrombosis and Haemostasis, 9, pp. 834-843; Berman, H., Henrick, K., Nakamura, H., Announcing the worldwide protein data bank (2003) Nature Structural Biology, 10, p. 980; Berman, H., Henrick, K., Nakamura, H., Markley, J.L., The worldwide Protein Data Bank (wwPDB): Ensuring a single, uniform archive of PDB data (2007) Nucleic Acids Research, 35, pp. D301-D303; Bernard, D., Quatannens, B., Vandenbunder, B., Abbadie, C., Rel/NF-kappaB transcription factors protect against tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by up-regulating the TRAIL decoy receptor DcR1 (2001) The Journal of Biological Chemistry, 276, pp. 27322-27328; Bernardi, S., Bossi, F., Toffoli, B., Fabris, B., Roles and clinical applications of OPG and TRAIL as biomarkers in cardiovascular disease (2016) BioMed Research International, 2016, p. 1752854; Bernardi, S., Toffoli, B., Bossi, F., Candido, R., Stenner, E., Carretta, R., Fabris, B., Circulating osteoprotegerin is associated with chronic kidney disease in hypertensive patients (2017) BMC Nephrology, 18, p. 219; Bonnet, N., Garnero, P., Ferrari, S., Periostin action in bone (2016) Molecular and Cellular Endocrinology, 432, pp. 75-82; Boorsma, C.E., Draijer, C., Cool, R.H., Brandsma, C., Nossent, G., Brass, D.M., Melgert, B.N., A possible role for the RANK/RANKL/OPG axis in pulmonary fibrosis (2014) American Journal of Respiratory and Critical Care Medicine, 189, p. A1252; Bord, S., Ireland, D.C., Beavan, S.R., Compston, J.E., The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts (2003) Bone, 32, pp. 136-141; Bosselut, N., Taibi, L., Guéchot, J., Zarski, J.P., Sturm, N., Gelineau, M.C., Vaubourdolle, M., Including osteoprotegerin and collagen IV in a score-based blood test for liver fibrosis increases diagnostic accuracy (2013) Clinica Chimica Acta, 415, pp. 63-68; Boyce, B.F., Xing, L., Biology of RANK, RANKL, and osteoprotegerin (2007) Arthritis Research & Therapy, 9, p. S1; Boyce, B.F., Xing, L., Functions of RANKL/RANK/OPG in bone modeling and remodeling (2008) Archives of Biochemistry and Biophysics, 473, pp. 139-146; Brass, D.M., McGee, S.P., Dunkel, M.K., Reilly, S.M., Tobolewski, J.M., Sabo-Attwood, T., Fattman, C.L., Gender influences the response to experimental silica-induced lung fibrosis in mice (2010) American Journal of Physiology. Lung Cellular and Molecular Physiology, 299, pp. L664-L671; Brass, D.M., Yang, I.V., Kennedy, M.P., Whitehead, G.S., Rutledge, H., Burch, L.H., Schwartz, D.A., Fibroproliferation in LPS-induced airway remodeling and bleomycin-induced fibrosis share common patterns of gene expression (2008) Immunogenetics, 60, pp. 353-369; Burgess, J.K., Mauad, T., Tjin, G., Karlsson, J.C., Westergren-Thorsson, G., The extracellular matrix – The under-recognized element in lung disease? (2016) The Journal of Pathology, 240, pp. 397-409; Callegari, A., Coons, M.L., Ricks, J.L., Rosenfeld, M.E., Scatena, M., Increased calcification in osteoprotegerin-deficient smooth muscle cells: Dependence on receptor activator of NF-kappaB ligand and interleukin 6 (2014) Journal of Vascular Research, 51, pp. 118-131; Caminati, A., Cassandro, R., Torre, O., Harari, S., Severe idiopathic pulmonary fibrosis: What can be done? (2017) European Respiratory Review, 26; Cao, F., Liu, X., Cao, X., Wang, S., Fu, K., Zhao, Y., Liu, J., Fibroblast growth factor 21 plays an inhibitory role in vascular calcification in vitro through OPG/RANKL system (2017) Biochemical and Biophysical Research Communications, 491, pp. 578-586; Castellanos-Gonzalez, A., Yancey, L.S., Wang, H.C., Pantenburg, B., Liscum, K.R., Lewis, D.E., White, A.C., Jr., Cryptosporidium infection of human intestinal epithelial cells increases expression of osteoprotegerin: A novel mechanism for evasion of host defenses (2008) The Journal of Infectious Diseases, 197, pp. 916-923; Cha, S.S., Kim, M.S., Choi, Y.H., Sung, B.J., Shin, N.K., Shin, H.C., Oh, B.H., 2.8 A resolution crystal structure of human TRAIL, a cytokine with selective antitumor activity (1999) Immunity, 11, pp. 253-261; Chanda, D., Otoupalova, E., Smith, S.R., Volckaert, T., De Langhe, S.P., Thannickal, V.J., Developmental pathways in the pathogenesis of lung fibrosis (2019) Molecular Aspects of Medicine, 65, pp. 56-69; Chen, P., Parks, W.C., Role of matrix metalloproteinases in epithelial migration (2009) Journal of Cellular Biochemistry, 108, pp. 1233-1243; Chen, S., Fu, L., Raja, S.M., Yue, P., Khuri, F.R., Sun, S.Y., Dissecting the roles of DR4, DR5 and c-FLIP in the regulation of geranylgeranyltransferase I inhibition-mediated augmentation of TRAIL-induced apoptosis (2010) Molecular Cancer, 9, p. 23; Chirinos, J.A., Orlenko, A., Zhao, L., Basso, M.D., Cvijic, M.E., Li, Z., Cappola, T.P., Multiple plasma biomarkers for risk stratification in patients with heart failure and preserved ejection fraction (2020) Journal of the American College of Cardiology, 75, pp. 1281-1295; Corisdeo, S., Gyda, M., Zaidi, M., Moonga, B.S., Troen, B.R., New insights into the regulation of cathepsin K gene expression by osteoprotegerin ligand (2001) Biochemical and Biophysical Research Communications, 285, pp. 335-339; Costanza, B., Umelo, I.A., Bellier, J., Castronovo, V., Turtoi, A., Stromal modulators of TGF-beta in cancer (2017) Journal of Clinical Medicine, 6; Crowder, R.N., Dicker, D.T., El-Deiry, W.S., The deubiquitinase inhibitor PR-619 sensitizes normal human fibroblasts to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cell death (2016) The Journal of Biological Chemistry, 291, pp. 5960-5970; Davenport, C., Harper, E., Rochfort, K.D., Forde, H., Smith, D., Cummins, P.M., RANKL inhibits the production of osteoprotegerin from smooth muscle cells under basal conditions and following exposure to cyclic strain (2018) Journal of Vascular Research, 55, pp. 111-123; Demedts, M., Wells, A.U., Anto, J.M., Costabel, U., Hubbard, R., Cullinan, P., Taylor, A.N., Interstitial lung diseases: An epidemiological overview (2001) The European Respiratory Journal. Supplement, 32, pp. 2s-16s; Di Bartolo, B.A., Cartland, S.P., Harith, H.H., Bobryshev, Y.V., Schoppet, M., Kavurma, M.M., TRAIL-deficiency accelerates vascular calcification in atherosclerosis via modulation of RANKL (2013) PLoS One, 8; Distler, J.H.W., Györfi, A.-H., Ramanujam, M., Whitfield, M.L., Königshoff, M., Lafyatis, R., Shared and distinct mechanisms of fibrosis (2019) Nature Reviews Rheumatology, 15, pp. 705-730; Duan, P., Bonewald, L.F., The role of the wnt/beta-catenin signaling pathway in formation and maintenance of bone and teeth (2016) The International Journal of Biochemistry & Cell Biology, 77, pp. 23-29; Dumnicka, P., Zylka, A., Kusnierz-Cabala, B., Gurda-Duda, A., Kuzniewski, M., Drozdz, R., Kulig, J., Osteoprotegerin, trail and osteoprotegerin/trail ratio in patients at early phase of acute pancreatitis (2014) Folia Medica Cracoviensia, 54, pp. 17-26; Fábrega, E., Orive, A., García-Suarez, C., García-Unzueta, M., Antonio Amado, J., Pons-Romero, F., Osteoprotegerin and RANKL in alcoholic liver cirrhosis (2005) Liver International, 25, pp. 305-310; Fan, Z., Guan, J., Antifibrotic therapies to control cardiac fibrosis (2016) Biomaterials Research, 20, p. 13; Feng, W., Li, W., Liu, W., Wang, F., Li, Y., Yan, W., IL-17 induces myocardial fibrosis and enhances RANKL/OPG and MMP/TIMP signaling in isoproterenol-induced heart failure (2009) Experimental and Molecular Pathology, 87, pp. 212-218; Fennen, M., Pap, T., Dankbar, B., Smad-dependent mechanisms of inflammatory bone destruction (2016) Arthritis Research & Therapy, 18, p. 279; Fingleton, B., Matrix metalloproteinases as regulators of inflammatory processes (2017) Biochimica et Biophysica Acta (BBA) – Molecular Cell Research, 1864, pp. 2036-2042; Galli, C., Piergianni, M., Piemontese, M., Lumetti, S., Ravanetti, F., Cacchioli, A., Passeri, G., Periostin improves cell adhesion to implantable biomaterials and osteoblastic differentiation on implant titanium surfaces in a topography-dependent fashion (2014) Journal of Biomedical Materials Research Part A, 102, pp. 3855-3861; García-Valdecasas-Campelo, E., González-Reimers, E., Santolaria-Fernández, F., De la Vega-Prieto, M.J., Milena-Abril, A., Sánchez-Pérez, M.J., Gómez-Rodríguez Mde, L., Serum osteoprotegerin and RANKL levels in chronic alcoholic liver disease (2006) Alcohol and Alcoholism, 41, pp. 261-266; Ge, P.S., Runyon, B.A., Treatment of patients with cirrhosis (2016) The New England Journal of Medicine, 375, pp. 2104-2105; Geerts, D., Chopra, C., Connelly, L., Osteoprotegerin: Relationship to breast cancer risk and prognosis (2020) Frontiers in Oncology, 10, p. 462; Giannandrea, M., Parks, W.C., Diverse functions of matrix metalloproteinases during fibrosis (2014) Disease Models & Mechanisms, 7, pp. 193-203; Gomez-Benito, M., Martinez-Lorenzo, M.J., Anel, A., Marzo, I., Naval, J., Membrane expression of DR4, DR5 and caspase-8 levels, but not Mcl-1, determine sensitivity of human myeloma cells to Apo2L/TRAIL (2007) Experimental Cell Research, 313, pp. 2378-2388; González-Calvin, J.L., Mundi, J.L., Casado-Caballero, F.J., Abadia, A.C., Martin-Ibañez, J.J., Bone mineral density and serum levels of soluble tumor necrosis factors, estradiol, and osteoprotegerin in postmenopausal women with cirrhosis after viral hepatitis (2009) The Journal of Clinical Endocrinology and Metabolism, 94, pp. 4844-4850; González-González, L., Alonso, J., Periostin: A matricellular protein with multiple functions in cancer development and progression (2018) Frontiers in Oncology, 8; Goswami, S., Sharma-Walia, N., Osteoprotegerin rich tumor microenvironment: Implications in breast cancer (2016) Oncotarget, 7, pp. 42777-42791; Gottwald, L., Piekarski, J., Kubiak, R., Szwalski, J., Pasz-Walczak, G., Sek, P., Jeziorski, A., Membrane expression of TRAIL receptors DR4, DR5, DcR1 and DcR2 in the normal endometrium, atypical endometrial hyperplasia and endometrioid adenocarcinoma: A tissue microarray study (2013) Archives of Gynecology and Obstetrics, 288, pp. 889-899; Guañabens, N., Enjuanes, A., Alvarez, L., Peris, P., Caballería, L., Jesús Martínez de Osaba, M., Parés, A., High osteoprotegerin serum levels in primary biliary cirrhosis are associated with disease severity but not with the mRNA gene expression in liver tissue (2009) Journal of Bone and Mineral Metabolism, 27, pp. 347-354; Guicciardi, M.E., Malhi, H., Mott, J.L., Gores, G.J., Apoptosis and necrosis in the liver (2013) Comprehensive Physiology, 3, pp. 977-1010; Habibie, H., Putri, K., Boorsma, C.E., Brass, D., Heukels, P., Wijsenbeek-Lourens, M., Melgert, B.N., Osteoprotegerin is elevated in pulmonary fibrosis and associates with IPF progression (2020) bioRxiv; Hackl, N.J., Bersch, C., Feick, P., Antoni, C., Franke, A., Singer, M.V., Nakchbandi, I.A., Circulating fibronectin isoforms predict the degree of fibrosis in chronic hepatitis C (2010) Scandinavian Journal of Gastroenterology, 45, pp. 349-356; Hao, Y., Tsuruda, T., Sekita-Hatakeyama, Y., Kurogi, S., Kubo, K., Sakamoto, S., Kitamura, K., Cardiac hypertrophy is exacerbated in aged mice lacking the osteoprotegerin gene (2016) Cardiovascular Research, 110, pp. 62-72; Harashima, S.I., Tsukamoto, H., Horiuchi, T., Osteoprotegerin and receptor activator of nuclear factor kappaB ligand expression in fibroblast-like synoviocytes from rheumatoid arthritis and osteoarthritis patients (2004) Rheumatology (Oxford), 43, pp. 396-397. , author reply 397; Herbertz, S., Sawyer, J.S., Stauber, A.J., Gueorguieva, I., Driscoll, K.E., Estrem, S.T., Lahn, M.M., Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway (2015) Drug Design, Development and Therapy, 9, pp. 4479-4499; Hernandez-Gea, V., Friedman, S.L., Pathogenesis of liver fibrosis (2011) Annual Review of Pathology, 6, pp. 425-456; Herrera, I., Cisneros, J., Maldonado, M., Ramírez, R., Ortiz-Quintero, B., Anso, E., Pardo, A., Matrix metalloproteinase (MMP)-1 induces lung alveolar epithelial cell migration and proliferation, protects from apoptosis, and represses mitochondrial oxygen consumption* (2013) Journal of Biological Chemistry, 288, pp. 25964-25975; Herrera, J., Henke, C.A., Bitterman, P.B., Extracellular matrix as a driver of progressive fibrosis (2018) The Journal of Clinical Investigation, 128, pp. 45-53; Hinz, B., Tissue stiffness, latent TGF-beta1 activation, and mechanical signal transduction: Implications for the pathogenesis and treatment of fibrosis (2009) Current Rheumatology Reports, 11, pp. 120-126; Holen, I., Cross, S.S., Neville-Webbe, H.L., Cross, N.A., Balasubramanian, S.P., Croucher, P.I., Eaton, C.L., Osteoprotegerin (OPG) expression by breast cancer cells in vitro and breast tumours in vivo–A role in tumour cell survival? (2005) Breast Cancer Research and Treatment, 92, pp. 207-215; Hosbond, S.E., Poulsen, T.S., Diederichsen, A.C., Nybo, M., Rasmussen, L.M., Mickley, H., Osteoprotegerin as a marker of atherosclerosis: A systematic update (2012) Scandinavian Cardiovascular Journal, 46, pp. 203-211; Infante, M., Fabi, A., Cognetti, F., Gorini, S., Caprio, M., Fabbri, A., RANKL/RANK/OPG system beyond bone remodeling: Involvement in breast cancer and clinical perspectives (2019) Journal of Experimental & Clinical Cancer Research, 38, p. 12; Ismail, M.H., Pinzani, M., Reversal of liver fibrosis (2009) Saudi Journal of Gastroenterology, 15, pp. 72-79; Jaffar, J., Unger, S., Corte, T.J., Keller, M., Wolters, P.J., Richeldi, L., Burgess, J.K., Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis (2014) Chest, 146, pp. 1055-1063; Janssens, K., ten Dijke, P., Janssens, S., Van Hul, W., Transforming growth factor-beta1 to the bone (2005) Endocrine Reviews, 26, pp. 743-774; Jia, D., Zhu, Q., Liu, H., Zuo, C., He, Y., Chen, G., Lu, A., Osteoprotegerin disruption attenuates HySu-induced pulmonary hypertension through integrin alphavbeta3/FAK/AKT pathway suppression (2017) Circulation. Cardiovascular Genetics, 10; Jia, J., Zhou, H., Zeng, X., Feng, S., Estrogen stimulates osteoprotegerin expression via the suppression of miR-145 expression in MG-63 cells (2017) Molecular Medicine Reports, 15, pp. 1539-1546; Jones, D.H., Kong, Y.Y., Penninger, J.M., Role of RANKL and RANK in bone loss and arthritis (2002) Annals of the Rheumatic Diseases, 61, pp. ii32-39; Kamimura, D., Suzuki, T., Furniss, A.L., Griswold, M.E., Kullo, I.J., Lindsey, M.L., Hall, M.E., Elevated serum osteoprotegerin is associated with increased left ventricular mass index and myocardial stiffness (2017) Journal of Cardiovascular Medicine, 18, pp. 954-961; Karsdal, M.A., Manon-Jensen, T., Genovese, F., Kristensen, J.H., Nielsen, M.J., Sand, J.M., Schuppan, D., Novel insights into the function and dynamics of extracellular matrix in liver fibrosis (2015) American Journal of Physiology. Gastrointestinal and Liver Physiology, 308, pp. G807-G830; Katopodis, H., Philippou, A., Tenta, R., Doillon, C., Papachroni, K.K., Papavassiliou, A.G., Koutsilieris, M., MG-63 osteoblast-like cells enhance the osteoprotegerin expression of PC-3 prostate cancer cells (2009) Anticancer Research, 29, pp. 4013-4018; Kavurma, M.M., Tan, N.Y., Bennett, M.R., Death receptors and their ligands in atherosclerosis (2008) Arteriosclerosis, Thrombosis, and Vascular Biology, 28, pp. 1694-1702; Kazama, J.J., Shigematsu, T., Yano, K., Tsuda, E., Miura, M., Iwasaki, Y., Fukagawa, M., Increased circulating levels of osteoclastogenesis inhibitory factor (osteoprotegerin) in patients with chronic renal failure (2002) American Journal of Kidney Diseases, 39, pp. 525-532; Kim, E.J., Cho, H.J., Park, D., Kim, J.Y., Kim, Y.B., Park, T.G., Oh, Y.K., Antifibrotic effect of MMP13-encoding plasmid DNA delivered using polyethylenimine shielded with hyaluronic acid (2011) Molecular Therapy, 19, pp. 355-361; Kobayashi, Y., Uehara, S., Udagawa, N., Takahashi, N., Regulation of bone metabolism by Wnt signals (2016) Journal of Biochemistry, 159, pp. 387-392; Kong, P., Christia, P., Frangogiannis, N.G., The pathogenesis of cardiac fibrosis (2014) Cellular and Molecular Life Sciences: CMLS, 71, pp. 549-574; Kovacs, B., Vajda, E., Nagy, E.E., Regulatory effects and interactions of the Wnt and OPG-RANKL-RANK signaling at the bone-cartilage interface in osteoarthritis (2019) International Journal of Molecular Sciences, 20; Kramer, I., Halleux, C., Keller, H., Pegurri, M., Gooi, J.H., Weber, P.B., Kneissel, M., Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis (2010) Molecular and Cellular Biology, 30, pp. 3071-3085; Kuzniewski, M., Fedak, D., Dumnicka, P., Stepien, E., Kusnierz-Cabala, B., Cwynar, M., Sulowicz, W., Osteoprotegerin and osteoprotegerin/TRAIL ratio are associated with cardiovascular dysfunction and mortality among patients with renal failure (2016) Advances in Medical Sciences, 61, pp. 269-275; Labovsky, V., Vallone, V.B., Martinez, L.M., Otaegui, J., Chasseing, N.A., Expression of osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, tumor necrosis factor-related apoptosis-inducing ligand, stromal cell-derived factor-1 and their receptors in epithelial metastatic breast cancer cell lines (2012) Cancer Cell International, 12, p. 29; Lamora, A., Talbot, J., Mullard, M., Brounais-Le Royer, B., Redini, F., Verrecchia, F., TGF-beta signaling in bone remodeling and osteosarcoma progression (2016) Journal of Clinical Medicine, 5; Lan, T.-H., Huang, X.-Q., Tan, H.-M., Vascular fibrosis in atherosclerosis (2013) Cardiovascular Pathology, 22, pp. 401-407; Landry, N.M., Cohen, S., Dixon, I.M.C., Periostin in cardiovascular disease and development: A tale of two distinct roles (2017) Basic Research in Cardiology, 113, p. 1; Lane, D., Matte, I., Laplante, C., Garde-Granger, P., Rancourt, C., Piche, A., Osteoprotegerin (OPG) activates integrin, focal adhesion kinase (FAK), and Akt signaling in ovarian cancer cells to attenuate TRAIL-induced apoptosis (2013) Journal of Ovarian Research, 6, p. 82; Lane, D., Matte, I., Rancourt, C., Piche, A., Osteoprotegerin (OPG) protects ovarian cancer cells from TRAIL-induced apoptosis but does not contribute to malignant ascites-mediated attenuation of TRAIL-induced apoptosis (2012) Journal of Ovarian Research, 5, p. 34; Lee, G.L., Yeh, C.C., Wu, J.Y., Lin, H.C., Wang, Y.F., Kuo, Y.Y., Kuo, C.C., TLR2 promotes vascular smooth muscle cell chondrogenic differentiation and consequent calcification via the concerted actions of osteoprotegerin suppression and IL-6-Mediated RANKL induction (2019) Arteriosclerosis, Thrombosis, and Vascular Biology, 39, pp. 432-445; Lee, K.S., Lee, S.J., Park, H.J., Chung, J.P., Han, K.H., Chon, C.Y., Moon, Y.M., Oxidative stress effect on the activation of hepatic stellate cells (2001) Yonsei Medical Journal, 42, pp. 1-8; Lee, S.B., Kalluri, R., Mechanistic connection between inflammation and fibrosis (2010) Kidney International, pp. S22-S26; Lee, U.E., Friedman, S.L., Mechanisms of hepatic fibrogenesis (2011) Best Practice & Research. Clinical Gastroenterology, 25, pp. 195-206; Lewis, J.R., Lim, W.H., Zhu, K., Wong, G., Dhaliwal, S.S., Lim, E.M., Prince, R.L., Elevated osteoprotegerin predicts declining renal function in elderly women: A 10-year prospective cohort study (2014) American Journal of Nephrology, 39, pp. 66-74; Lippi, G., Cervellin, G., Risk assessment of post-infarction heart failure. Systematic review on the role of emerging biomarkers (2014) Critical Reviews in Clinical Laboratory Sciences, 51, pp. 13-29; Liu, G., Cooley, M.A., Jarnicki, A.G., Borghuis, T., Nair, P.M., Tjin, G., Hansbro, P.M., Fibulin-1c regulates transforming growth factor-beta activation in pulmonary tissue fibrosis (2019) JCI Insight, 5; Liu, G., Cooley, M.A., Jarnicki, A.G., Hsu, A.C., Nair, P.M., Haw, T.J., Hansbro, P.M., Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases (2016) JCI Insight, 1; Liu, L.N., Mao, Y.M., Zhao, C.N., Wang, H., Yuan, F.F., Li, X.M., Pan, H.F., Circulating levels of osteoprotegerin, osteocalcin and osteopontin in patients with rheumatoid arthritis: A systematic review and meta-analysis (2019) Immunological Investigations, 48, pp. 107-120; Liu, W., Feng, W., Wang, F., Li, W., Gao, C., Zhou, B., Ma, M., Osteoprotegerin/RANK/RANKL axis in cardiac remodeling due to immuno-inflammatory myocardial disease (2008) Experimental and Molecular Pathology, 84, pp. 213-217; Liu, W., Zhang, X., Receptor activator of nuclear factor-kappaB ligand (RANKL)/RANK/osteoprotegerin system in bone and other tissues (review) (2015) Molecular Medicine Reports, 11, pp. 3212-3218; Loudon, B.L., Ntatsaki, E., Newsome, S., Halliday, B., Lota, A., Ali, A., Prasad, S.K., Osteoprotegerin and myocardial fibrosis in patients with aortic stenosis (2018) Scientific Reports, 8, p. 14550; Luan, X., Lu, Q., Jiang, Y., Zhang, S., Wang, Q., Yuan, H., Wang, X., Crystal structure of human RANKL complexed with its decoy receptor osteoprotegerin (2012) The Journal of Immunology, 189, pp. 245-252; Ludbrook, S.B., Barry, S.T., Delves, C.J., Horgan, C.M., The integrin alphavbeta3 is a receptor for the latency-associated peptides of transforming growth factors beta1 and beta3 (2003) The Biochemical Journal, 369, pp. 311-318; Majewski, S., Zhou, X., Miłkowska-Dymanowska, J., Białas, A.J., Piotrowski, W.J., Malinovschi, A., Proteomic profiling of peripheral blood and bronchoalveolar lavage fluid in interstitial lung diseases: An explorative study (2021) ERJ Open Research, 7, pp. 00489-02020; Malara, A., Gruppi, C., Massa, M., Rosti, V., Barosi, G., Balduini, A., Plasma EDA fibronectin in primary myelofibrosis correlates with bone marrow fibrosis and predicts splenomegaly (2019) Blood, 134, p. 1688; Mangan, S.H., Van Campenhout, A., Rush, C., Golledge, J., Osteoprotegerin upregulates endothelial cell adhesion molecule response to tumor necrosis factor-alpha associated with induction of angiopoietin-2 (2007) Cardiovascular Research, 76, pp. 494-505; Maniatis, K., Siasos, G., Oikonomou, E., Vavuranakis, M., Zaromytidou, M., Mourouzis, K., Tousoulis, D., Osteoprotegerin and osteopontin serum levels are associated with vascular function and inflammation in coronary artery disease patients (2020) Current Vascular Pharmacology, 18, pp. 523-530; Mannello, F., Luchetti, F., Falcieri, E., Papa, S., Multiple roles of matrix metalloproteinases during apoptosis (2005) Apoptosis, 10, pp. 19-24; Marshall, R.P., Simpson, J.K., Lukey, P.T., Strategies for biomarker discovery in fibrotic disease (2013) Biochimica et Biophysica Acta, 1832, pp. 1079-1087; Martinez, F.J., Chisholm, A., Collard, H.R., Flaherty, K.R., Myers, J., Raghu, G., Richeldi, L., The diagnosis of idiopathic pulmonary fibrosis: Current and future approaches (2017) The Lancet Respiratory Medicine, 5, pp. 61-71; McGonigle, J.S., Giachelli, C.M., Scatena, M., Osteoprotegerin and RANKL differentially regulate angiogenesis and endothelial cell function (2009) Angiogenesis, 12, pp. 35-46; McMahon, G.A., Dignam, J.D., Gentry, L.E., Structural characterization of the latent complex between transforming growth factor beta 1 and beta 1-latency-associated peptide (1996) The Biochemical Journal, 313, pp. 343-351; Meng, H., Bai, X., Yu, H., Wang, Z., Guo, A., Osteoprotegerin promotes cell growth by regulating matrix metalloprotease-13 in chondrocytes (2017) Journal of Biomaterials and Tissue Engineering, 7, pp. 257-260; Meng, X.-M., Nikolic-Paterson, D.J., Lan, H.Y., Inflammatory processes in renal fibrosis (2014) Nature Reviews Nephrology, 10, pp. 493-503; Mielczarek-Palacz, A., Kondera-Anasz, Z., Smycz-Kubanska, M., Changes in the concentration of markers participating in the regulation of the apoptosis receptor pathway involving soluble tumour necrosis factor ligand inducing apoptosis (sTRAIL) and osteoprotegerin (OPG) in the serum of women with ovarian cancer-participation in pathogenesis or a possible clinical use? (2020) Cells, 9; Miyashita, T., Kawakami, A., Nakashima, T., Yamasaki, S., Tamai, M., Tanaka, F., Eguchi, K., Osteoprotegerin (OPG) acts as an endogenous decoy receptor in tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis of fibroblast-like synovial cells (2004) Clinical and Experimental Immunology, 137, pp. 430-436; Monegal, A., Navasa, M., Peris, P., Alvarez, L., Pons, F., Rodés, J., Guañabens, N., Serum osteoprotegerin and its ligand in cirrhotic patients referred for orthotopic liver transplantation: Relationship with metabolic bone disease (2007) Liver International, 27, pp. 492-497; Moschen, A.R., Kaser, A., Stadlmann, S., Millonig, G., Kaser, S., Mühllechner, P., Tilg, H., The RANKL/OPG system and bone mineral density in patients with chronic liver disease (2005) Journal of Hepatology, 43, pp. 973-983; Mosheimer, B.A., Kaneider, N.C., Feistritzer, C., Djanani, A.M., Sturn, D.H., Patsch, J.R., Wiedermann, C.J., Syndecan-1 is involved in osteoprotegerin-induced chemotaxis in human peripheral blood monocytes (2005) The Journal of Clinical Endocrinology and Metabolism, 90, pp. 2964-2971; Mu, D., Cambier, S., Fjellbirkeland, L., Baron, J.L., Munger, J.S., Kawakatsu, H., Nishimura, S.L., The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1 (2002) The Journal of Cell Biology, 157, pp. 493-507; Münch, J., Abdelilah-Seyfried, S., Sensing and responding of cardiomyocytes to changes of tissue stiffness in the diseased heart (2021) Frontiers in Cell and Development Biology, 9, p. 642840; Munger, J.S., Harpel, J.G., Giancotti, F.G., Rifkin, D.B., Interactions between growth factors and integrins: Latent forms of transforming growth factor-beta are ligands for the integrin alphavbeta1 (1998) Molecular Biology of the Cell, 9, pp. 2627-2638; Munger, J.S., Huang, X., Kawakatsu, H., Griffiths, M.J., Dalton, S.L., Wu, J., Sheppard, D., The integrin alpha v beta 6 binds and activates latent TGF beta 1: A mechanism for regulating pulmonary inflammation and fibrosis (1999) Cell, 96, pp. 319-328; Muro, A.F., Moretti, F.A., Moore, B.B., Yan, M., Atrasz, R.G., Wilke, C.A., White, E.S., An essential role for fibronectin extra type III domain A in pulmonary fibrosis (2008) American Journal of Respiratory and Critical Care Medicine, 177, pp. 638-645; Musialik, K., Szulinska, M., Hen, K., Skrypnik, D., Bogdanski, P., The relation between osteoprotegerin, inflammatory processes, and atherosclerosis in patients with metabolic syndrome (2017) European Review for Medical and Pharmacological Sciences, 21, pp. 4379-4385; Nakahara, T., Kawai-Kowase, K., Matsui, H., Sunaga, H., Utsugi, T., Iso, T., Kurabayashi, M., Fibroblast growth factor 23 inhibits osteoblastic gene expression and induces osteoprotegerin in vascular smooth muscle cells (2016) Atherosclerosis, 253, pp. 102-110; Nanda, K.S., Brady, J.J., Murray, B.F., Sullivan, O., Fearon, U., McKenna, M.J., Ryan, E.J., Elevated circulating osteoprotegerin and reduced matrix-metalloprotease-9 in post-menopausal women with chronic Hepatitis C virus infection (2012) Cytokine, 60, pp. 328-333; Naumnik, W., Naumnik, B., Niklinska, W., Ossolinska, M., Chyczewska, E., Osteoprotegerin/sRANKL signaling system in pulmonary sarcoidosis: A bronchoalveolar lavage study (2017) Advances in Experimental Medicine and Biology, 944, pp. 1-7; Newby, A.C., Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates (2006) Cardiovascular Research, 69, pp. 614-624; Nkyimbeng, T., Ruppert, C., Shiomi, T., Dahal, B., Lang, G., Seeger, W., Günther, A., Pivotal role of matrix metalloproteinase 13 in extracellular matrix turnover in idiopathic pulmonary fibrosis (2013) PLoS One, 8; Okamoto, M., Hoshino, T., Kitasato, Y., Sakazaki, Y., Kawayama, T., Fujimoto, K., Aizawa, H., Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias (2011) European Respiratory Journal, 37, p. 1119; Okamoto, M., Izuhara, K., Ohta, S., Ono, J., Hoshino, T., Ability of periostin as a new biomarker of idiopathic pulmonary fibrosis (2019) Advances in Experimental Medicine and Biology, 1132, pp. 79-87; Ong, J., Timens, W., Rajendran, V., Algra, A., Spira, A., Lenburg, M.E., Brandsma, C.A., Identification of transforming growth factor-beta-regulated microRNAs and the microRNA-targetomes in primary lung fibroblasts (2017) PLoS One, 12; Ono, T., Hayashi, M., Sasaki, F., Nakashima, T., RANKL biology: Bone metabolism, the immune system, and beyond (2020) Inflamm Regen, 40, p. 2; Park, J.H., Lee, N.K., Lee, S.Y., Current understanding of RANK signaling in osteoclast differentiation and maturation (2017) Molecules and Cells, 40, pp. 706-713; Pellicoro, A., Ramachandran, P., Iredale, J.P., Fallowfield, J.A., Liver fibrosis and repair: Immune regulation of wound healing in a solid organ (2014) Nature Reviews. Immunology, 14, pp. 181-194; Pritzker, L.B., Scatena, M., Giachelli, C.M., The role of osteoprotegerin and tumor necrosis factor-related apoptosis-inducing ligand in human microvascular endothelial cell survival (2004) Molecular Biology of the Cell, 15, pp. 2834-2841; Prystupa, A., Dąbrowska, A., Sak, J.J., Tarach, J., Toruń-Jurkowska, A., Lachowska-Kotowska, P., Dzida, G., Concentrations of fetuin-A, osteoprotegerin and α-Klotho in patients with alcoholic liver cirrhosis (2016) Experimental and Therapeutic Medicine, 12, pp. 3464-3470; Rachner, T.D., Benad, P., Rauner, M., Goettsch, C., Singh, S.K., Schoppet, M., Hofbauer, L.C., Osteoprotegerin production by breast cancer cells is suppressed by dexamethasone and confers resistance against TRAIL-induced apoptosis (2009) Journal of Cellular Biochemistry, 108, pp. 106-116; Raghu, G., Weycker, D., Edelsberg, J., Bradford, W.Z., Oster, G., Incidence and prevalence of idiopathic pulmonary fibrosis (2006) American Journal of Respiratory and Critical Care Medicine, 174, pp. 810-816; Ramachandran, P., Iredale, J.P., Macrophages: Central regulators of hepatic fibrogenesis and fibrosis resolution (2012) Journal of Hepatology, 56, pp. 1417-1419; Rimondi, E., di Iasio, M.G., Gonelli, A., Celeghini, C., Secchiero, P., Zauli, G., Hydrogen sulfide down-regulates the expression and release of osteoprotegerin (OPG) by vascular endothelial cells (2012) Investigational New Drugs, 30, pp. 1731-1735; Rizzardi, C., Leocata, P., Ventura, L., Zweyer, M., Brollo, A., Schneider, M., Melato, M., Apoptosis-related factors (TRAIL, DR4, DR5, DcR1, DcR2, apoptotic cells) and proliferative activity in ameloblastomas (2009) Anticancer Research, 29, pp. 1137-1142; Robbie, H., Daccord, C., Chua, F., Devaraj, A., Evaluating disease severity in idiopathic pulmonary fibrosis (2017) European Respiratory Review, 26; Robinson, M.W., Harmon, C., O’Farrelly, C., Liver immunology and its role in inflammation and homeostasis (2016) Cellular & Molecular Immunology, 13, pp. 267-276; Rochette, L., Meloux, A., Rigal, E., Zeller, M., Cottin, Y., Vergely, C., The role of osteoprotegerin in the crosstalk between vessels and bone: Its potential utility as a marker of cardiometabolic diseases (2018) Pharmacology & Therapeutics, 182, pp. 115-132; Rochette, L., Meloux, A., Rigal, E., Zeller, M., Cottin, Y., Vergely, C., The role of osteoprotegerin and its ligands in vascular function (2019) International Journal of Molecular Sciences, 20; Saika, M., Inoue, D., Kido, S., Matsumoto, T., 17beta-estradiol stimulates expression of osteoprotegerin by a mouse stromal cell line, ST-2, via estrogen receptor-alpha (2001) Endocrinology, 142, pp. 2205-2212; Sakata, M., Shiba, H., Komatsuzawa, H., Fujita, T., Ohta, K., Sugai, M., Kurihara, H., Expression of osteoprotegerin (osteoclastogenesis inhibitory factor) in cultures of human dental mesenchymal cells and epithelial cells (1999) Journal of Bone and Mineral Research, 14, pp. 1486-1492; Sandra, F., Hendarmin, L., Nakamura, S., Osteoprotegerin (OPG) binds with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL): Suppression of TRAIL-induced apoptosis in ameloblastomas (2006) Oral Oncology, 42, pp. 415-420; Sato, K., Niessner, A., Kopecky, S.L., Frye, R.L., Goronzy, J.R.J., Weyand, C.M., TRAIL-expressing T cells induce apoptosis of vascular smooth muscle cells in the atherosclerotic plaque (2006) Journal of Experimental Medicine, 203, pp. 239-250; Schubert, A., Schulz, H., Emons, G., Grundker, C., Expression of osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) in HCC70 breast cancer cells and effects of treatment with gonadotropin-releasing hormone on RANKL expression (2008) Gynecological Endocrinology, 24, pp. 331-338; Schuppan, D., Liver fibrosis: Common mechanisms and antifibrotic therapies (2015) Clinics and Research in Hepatology and Gastroenterology, 39, pp. S51-S59; Secchiero, P., Corallini, F., Rimondi, E., Chiaruttini, C., di Iasio, M.G., Rustighi, A., Zauli, G., Activation of the p53 pathway down-regulates the osteoprotegerin expression and release by vascular endothelial cells (2008) Blood, 111, pp. 1287-1294; Shetelig, C., Limalanathan, S., Eritsland, J., Hoffmann, P., Seljeflot, I., Gran, J.M., Andersen, G.O., Osteoprotegerin levels in ST-elevation myocardial infarction: Temporal profile and association with myocardial injury and left ventricular function (2017) PLoS One, 12; Standal, T., Seidel, C., Hjertner, O., Plesner, T., Sanderson, R.D., Waage, A., Sundan, A., Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells (2002) Blood, 100, pp. 3002-3007; van der Straaten, H.M., Canninga-van Dijk, M.R., Verdonck, L.F., Castigliego, D., Eric Borst, H.P., Aten, J., Fijnheer, R., Extra-domain-A fibronectin: A new marker of fibrosis in cutaneous graft-versus-host disease (2004) Journal of Investigative Dermatology, 123, pp. 1057-1062; Strieter, R.M., What differentiates normal lung repair and fibrosis? Inflammation, resolution of repair, and fibrosis (2008) Proceedings of the American Thoracic Society, 5, pp. 305-310; Szalay, F., Hegedus, D., Lakatos, P.L., Tornai, I., Bajnok, E., Dunkel, K., Lakatos, P., High serum osteoprotegerin and low RANKL in primary biliary cirrhosis (2003) Journal of Hepatology, 38, pp. 395-400; Thabut, G., Mal, H., Castier, Y., Groussard, O., Brugière, O., Marrash-Chahla, R., Fournier, M., Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis (2003) The Journal of Thoracic and Cardiovascular Surgery, 126, pp. 469-475; Toba, H., Lindsey, M.L., Extracellular matrix roles in cardiorenal fibrosis: Potential therapeutic targets for CVD and CKD in the elderly (2019) Pharmacology & Therapeutics, 193, pp. 99-120; Tobeiha, M., Moghadasian, M.H., Amin, N., Jafarnejad, S., RANKL/RANK/OPG pathway: A mechanism involved in exercise-induced bone remodeling (2020) BioMed Research International, 2020, p. 6910312; Toffoli, B., Pickering, R.J., Tsorotes, D., Wang, B., Bernardi, S., Kantharidis, P., Thomas, M.C., Osteoprotegerin promotes vascular fibrosis via a TGF-beta1 autocrine loop (2011) Atherosclerosis, 218, pp. 61-68; Tsochatzis, E.A., Bosch, J., Burroughs, A.K., Liver cirrhosis (2014) Lancet, 383, pp. 1749-1761; Tsuruda, T., Sekita-Hatakeyama, Y., Hao, Y., Sakamoto, S., Kurogi, S., Nakamura, M., Kitamura, K., Angiotensin II stimulation of cardiac hypertrophy and functional decompensation in osteoprotegerin-deficient mice (2016) Hypertension, 67, pp. 848-856; Tunyogi-Csapo, M., Kis-Toth, K., Radacs, M., Farkas, B., Jacobs, J.J., Finnegan, A., Glant, T.T., Cytokine-controlled RANKL and osteoprotegerin expression by human and mouse synovial fibroblasts: Fibroblast-mediated pathologic bone resorption (2008) Arthritis and Rheumatism, 58, pp. 2397-2408; Uchinami, H., Seki, E., Brenner, D.A., D’Armiento, J., Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis (2006) Hepatology, 44, pp. 420-429; Udagawa, N., Takahashi, N., Yasuda, H., Mizuno, A., Itoh, K., Ueno, Y., Suda, T., Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function (2000) Endocrinology, 141, pp. 3478-3484; Ueland, T., Yndestad, A., Øie, E., Florholmen, G., Halvorsen, B., Frøland, S.S., Aukrust, P., Dysregulated osteoprotegerin/RANK ligand/RANK axis in clinical and experimental heart failure (2005) Circulation, 111, pp. 2461-2468; Vandyke, K., Jackson, P., Rowe, A., Russell, P.J., Blair, J.M., Androgen decreases osteoprotegerin expression in prostate cancer cells (2007) Prostate Cancer and Prostatic Diseases, 10, pp. 160-166; Vidal, K., Serrant, P., Schlosser, B., van den Broek, P., Lorget, F., Donnet-Hughes, A., Osteoprotegerin production by human intestinal epithelial cells: A potential regulator of mucosal immune responses (2004) American Journal of Physiology. Gastrointestinal and Liver Physiology, 287, pp. G836-G844; Vitovski, S., Phillips, J.S., Sayers, J., Croucher, P.I., Investigating the interaction between osteoprotegerin and receptor activator of NF-kappaB or tumor necrosis factor-related apoptosis-inducing ligand: Evidence for a pivotal role for osteoprotegerin in regulating two distinct pathways (2007) The Journal of Biological Chemistry, 282, pp. 31601-31609; Wang, P., Li, S., Liu, L.N., Lv, T.T., Li, X.M., Li, X.P., Pan, H.F., Circulating osteoprotegerin levels are elevated in rheumatoid arthritis: A systematic review and meta-analysis (2017) Clinical Rheumatology, 36, pp. 2193-2200; Wang, S., El-Deiry, W.S., TRAIL and apoptosis induction by TNF-family death receptors (2003) Oncogene, 22, pp. 8628-8633; Wang, Y., Michiels, T., Setroikromo, R., van Merkerk, R., Cool, R.H., Quax, W.J., Creation of RANKL mutants with low affinity for decoy receptor OPG and their potential anti-fibrosis activity (2019) The FEBS Journal, 286, pp. 3582-3593; Weichhaus, M., Segaran, P., Renaud, A., Geerts, D., Connelly, L., Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis (2014) Cancer Medicine, 3, pp. 1112-1125; Weiskirchen, R., Weiskirchen, S., Tacke, F., Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications (2019) Molecular Aspects of Medicine, 65, pp. 2-15; Weivoda, M.M., Ruan, M., Pederson, L., Hachfeld, C., Davey, R.A., Zajac, J.D., Oursler, M.J., Osteoclast TGF-beta receptor signaling induces Wnt1 secretion and couples bone resorption to bone formation (2016) Journal of Bone and Mineral Research, 31, pp. 76-85; Wilson, M.S., Wynn, T.A., Pulmonary fibrosis: Pathogenesis, etiology and regulation (2009) Mucosal Immunology, 2, pp. 103-121; Wipff, P.J., Hinz, B., Integrins and the activation of latent transforming growth factor beta1 – An intimate relationship (2008) European Journal of Cell Biology, 87, pp. 601-615; Wong, N., Wang, X., miRDB: An online resource for microRNA target prediction and functional annotations (2015) Nucleic Acids Research, 43, pp. D146-D152; Wright, H.L., McCarthy, H.S., Middleton, J., Marshall, M.J., RANK, RANKL and osteoprotegerin in bone biology and disease (2009) Current Reviews in Musculoskeletal Medicine, 2, pp. 56-64; Wu, J., Zern, M.A., Hepatic stellate cells: A target for the treatment of liver fibrosis (2000) Journal of Gastroenterology, 35, pp. 665-672; Protein data bank: The single global archive for 3D macromolecular structure data (2019) Nucleic Acids Research, 47, pp. D520-D528; Wynn, T.A., Cellular and molecular mechanisms of fibrosis (2008) The Journal of Pathology, 214, pp. 199-210; Wynn, T.A., Integrating mechanisms of pulmonary fibrosis (2011) The Journal of Experimental Medicine, 208, pp. 1339-1350; Yang, M., Xu, D., Liu, Y., Guo, X., Li, W., Guo, C., Zhao, J., Combined serum biomarkers in non-invasive diagnosis of non-alcoholic steatohepatitis (2015) PLoS One, 10; Yilmaz, Y., Yonal, O., Kurt, R., Oral, A.Y., Eren, F., Ozdogan, O., Avsar, E., Serum levels of osteoprotegerin in the spectrum of nonalcoholic fatty liver disease (2010) Scandinavian Journal of Clinical and Laboratory Investigation, 70, pp. 541-546; Zannettino, A.C., Holding, C.A., Diamond, P., Atkins, G.J., Kostakis, P., Farrugia, A., Haynes, D.R., Osteoprotegerin (OPG) is localized to the Weibel-Palade bodies of human vascular endothelial cells and is physically associated with von Willebrand factor (2005) Journal of Cellular Physiology, 204, pp. 714-723; Zhong, J., Yang, H.-C., Fogo, A.B., A perspective on chronic kidney disease progression (2017) American Journal of Physiology. Renal Physiology, 312, pp. F375-F384; Ziffels, B., Ospel, J., Grün, K., Neri, D., Pfeil, A., Fritzenwanger, M., Franz, M., Detection of soluble ED-A(+) fibronectin and evaluation as novel serum biomarker for cardiac tissue remodeling (2016) Disease Markers, 2016, p. 3695454

Indexed by Scopus

Leave a Comment