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Ruiz-Zapata, A.M. (author), Heinz, A. (author), Kerkhof, M.H. (author), van de Westerlo-van Rijt, C. (author), Schmelzer, C.E.H. (author), Stoop, R. (author), Kluivers, K.B. (author), Oosterwijk, E. (author)Fibroblast to myofibroblast differentiation is a key feature of wound-healing in soft tissues, including the vagina. Vaginal fibroblasts maintain the integrity of the vaginal wall tissues, essential to keep pelvic organs in place and avoid pelvic organ prolapse (POP). The micro-environment of vaginal tissues in POP patients is stiffer and has...article 2020
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Morrison, M.C. (author), Kleemann, R. (author), van Koppen, A. (author), Hanemaaijer, R. (author), Verschuren, L. (author)Introduction: It is generally accepted that metabolic inflammation in the liver is an important driver of disease progression in NASH and associated matrix remodeling/fibrosis. However, the exact molecular inflammatory mechanisms are poorly defined in human studies. Investigation of key pathogenic mechanisms requires the use of pre-clinical...article 2018
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van Koppen, A. (author), Verschuren, L. (author), van den Hoek, A.M. (author), Verheij, J. (author), Morrison, M.C. (author), Li, K. (author), Nagabukuro, H. (author), Costessi, A. (author), Caspers, M.P.M. (author), van den Broek, T.J. (author), Sagartz, J. (author), Kluft, C. (author), Beysen, C. (author), Emson, C. (author), van Gool, A.J. (author), Goldschmeding, R. (author), Stoop, R. (author), Bobeldijk-Pastorova, I. (author), Turner, S.M. (author), Hanauer, G. (author), Hanemaaijer, R. (author)Background & Aims: The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for...article 2017
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Higuera, G.A. (author), Fernandes, H. (author), Spitters, T.W.G.M. (author), van de Peppel, J. (author), Aufferman, N. (author), Truckenmueller, R. (author), Stoop, R. (author), van Leeuwen, J.P. (author), de Boer, J. (author), Subramaniam, V. (author), Karperien, M. (author), van Blitterswijk, C. (author), van Boxtel, A. (author), Moroni, L. (author)Cells and tissues are intrinsically adapted to molecular gradients and use them to maintain or change their activity. The effect of such gradients is particularly important for cell populations that have an intrinsic capacity to differentiate into multiple cell lineages, such as bone marrow derived mesenchymal stromal cells (MSCs). Our results...article 2015
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Busnadiego, O. (author), Gorbenko del Blanco, D. (author), González-Santamaría, J. (author), Habashi, J.P. (author), Calderon, J.F. (author), Sandoval, P. (author), Bedja, D. (author), Guinea-Viniegra, J. (author), Lopez-Cabrera, M. (author), Rosell-Garcia, T. (author), Snabel, J.M. (author), Hanemaaijer, R. (author), Forteza, A. (author), Dietz, H.C. (author), Egea, G. (author), Rodriguez-Pascual, F. (author)Patients with Marfan syndrome (MFS) are at high risk of life-threatening aortic dissections. The condition is caused by mutations in the gene encoding fibrillin-1, an essential component in the formation of elastic fibers. While experimental findings in animal models of the disease have shown the involvement of transforming growth factor-β (TGF...article 2015
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Blaauboer, M.E. (author), Boeijen, F.R. (author), Emson, C.L. (author), Turner, S.M. (author), Zandieh-Doulabi, B. (author), Hanemaaijer, R. (author), Smit, T.H. (author), Stoop, R. (author), Everts, V. (author)Lung fibrosis is characterized by excessive deposition of extracellular matrix. This not only affects tissue architecture and function, but it also influences fibroblast behavior and thus disease progression. Here we describe the expression of elastin, type V collagen and tenascin C during the development of bleomycin-induced lung fibrosis. We...article 2014
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Neumann, A. (author), Berends, E.T.M. (author), Nerlich, A. (author), Molhoek, E.M. (author), Gallo, R.L. (author), Meerloo, T. (author), Nizet, V. (author), Naim, H.Y. (author), von Köckritz-Blickwede, M. (author)NETs (neutrophil extracellular traps) have been described as a fundamental innate immune defence mechanism. Duringformation of NETs, the nuclear membrane is disrupted by an asyet unknown mechanism. In the present study we investigated the role of human cathelicidin LL-37 in nuclear membrane disruption and formation of NETs. Immunofluorescence...article 2014
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Blaauboer, M.E. (author), Emson, C.L. (author), Verschuren, L. (author), van Erk, M. (author), Turner, S.M. (author), Everts, V. (author), Hanemaaijer, R. (author), Stoop, R. (author)Collagen deposition is a key process during idiopathic pulmonary fibrosis; however, little is known about the dynamics of collagen formation during disease development. Tissue samples of early stages of human disease are not readily available and it is difficult to identify changes in collagen content, since standard collagen analyses do not...article 2013
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Pons, D. (author), de Vries, F.R. (author), van den Elsen, P.J. (author), Heijmans, B.T. (author), Quax, P.H.A. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)Significant progress has been made in the clinical management of a variety of cardiovascular diseases. Nevertheless, the therapeutic efficacy of the current treatment modalities for atherosclerosis and restenosis is not fully sufficient in a large proportion of patients. One of the major contributing factors is the clinical and biological...article 2009
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Lu, Z.F. (author), Doulabi, B.Z. (author), Huang, C.L. (author), Bank, R.A. (author), Helder, M.N. (author), TNO Kwaliteit van Leven (author)β1 integrins play a controversial role during chondrogenesis. Since the maturation of chondrocytes relies on a signaling switch from cell-cell to cell-matrix interactions, we hypothesized that β1 integrins play a different role at the earlier (mainly cell-cell interaction) from the later stage (mainly cell-matrix interaction) of chondrogenesis....article 2008
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Bastiaansen-Jenniskens, Y.M. (author), Koevoet, W. (author), de Bart, A.C.W. (author), van der Linden, J.C. (author), Zuurmond, A.M. (author), Weinans, H. (author), Verhaar, J.A.N. (author), van Osch, G.J.V.M. (author), de Groot, J. (author), TNO Kwaliteit van Leven (author)Background: Damage to articular cartilage is one of the features of osteoarthritis (OA). Cartilage damage is characterised by a net loss of collagen and proteoglycans. The collagen network is considered highly important for cartilage function but little is known about processes that control composition and function of the cartilage collagen...article 2008
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Araujo, B.B. (author), Dolhnikoff, M. (author), Silva, L.F.F. (author), Elliot, J. (author), Lindeman, J.H.N. (author), Ferreira, D.S. (author), Mulder, A. (author), Gomes, H.A.P. (author), Fernezlian, S.M. (author), James, A. (author), Mauad, T. (author), TNO Kwaliteit van Leven (author)There is an intimate relationship between the extracellular matrix (ECM) and smooth muscle cells within the airways. Few studies have comprehensively assessed the composition of different ECM components and its regulators within the airway smooth muscle (ASM) in asthma. With the aid of image analysis, the fractional areas of total collagen and...article 2008
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Hoogendoorn, R. (author), Doulabi, B.Z. (author), Huang, C.L. (author), Wuisman, P.I. (author), Bank, R.A. (author), Helder, M.N. (author), TNO Kwaliteit van Leven (author)Study Design. Caprine lumbar intervertebral discs (IVD) were collected from previous studies and categorized as normal, mildly, or severely degenerated. The biochemical composition and the RNA profiles present in both the nucleus pulposus (NP) and the anulus fibrosus (AF) were analyzed. Objective. To determine the molecular changes occurring in...article 2008
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TNO Kwaliteit van Leven (author), Bastiaansen-Jenniskens, Y.M. (author), Koevoet, W. (author), de Bart, A.C.W. (author), Zuurmond, A.M. (author), Bank, R.A. (author), Verhaar, J.A.N. (author), de Groot, J. (author), van Osch, G.J.V.M. (author)Transforming growth factor beta (TGFbeta) is often used in cartilage tissue engineering to increase matrix formation by cells with various phenotypes. However, adverse effects of TGFbeta, such as extensive cross-linking in cultured fibroblasts, have also been reported. Our goal was to study effects of TGFbeta on collagen cross-linking and...article 2008
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Jansen, N.W.D. (author), Roosendaal, G. (author), Bijlsma, J.W.J. (author), de Groot, J. (author), Lafeber, F.P.J.G. (author), TNO Kwaliteit van Leven (author)Objective. Joint bleeding, or hemarthrosis, leads in time to severe joint damage. This study was carried out to test the in vitro thresholds of exposure time and concentration that lead to irreversible joint damage, to add to the discussion on the usefulness of aspiration of the joint after a hemorrhage. Methods. Explants of healthy human...article 2007
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TNO Kwaliteit van Leven (author), Hassane, S. (author), Claij, N. (author), Lantinga-van Leeuwen, I.S. (author), van Munsteren, J.C. (author), van Lent, N. (author), Hanemaaijer, R. (author), Breuning, M.H. (author), Peters, D.J.M. (author), de Ruiter, M.C. (author)OBJECTIVE - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multi-system disorder characterized by progressive cyst formation in the kidneys. Serious complications of ADPKD are intracranial and aortic aneurysms. The condition is mainly caused by mutations in the PKD1 or PKD2 gene. We have carefully analyzed vascular remodeling in...article 2007
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Jenniskens, Y.M. (author), Koevoet, W. (author), de Bart, A.C.W. (author), Weinans, H. (author), Jahr, H. (author), Verhaar, J.A.N. (author), de Groot, J. (author), van Osch, G.J.V.M. (author), TNO Kwaliteit van Leven (author)Objective: Examine effects of insulin-like growth factor 1 (IGF1), transforming growth factor β2 (TGFβ2) and fibroblast growth factor 2 (FGF2) on proteoglycan and collagen network and biomechanical properties of the newly formed cartilage matrix. Methods: Bovine articular chondrocytes were cultured in alginate beads for 3 weeks with or without...article 2006
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Valverde-Franco, G. (author), Binette, J.S. (author), Li, W. (author), Wang, H. (author), Chai, S. (author), Laflamme, F. (author), Tran-Khanh, N. (author), Quenneville, E. (author), Meijers, T. (author), Poole, A.R. (author), Mort, J.S. (author), Buschmann, M.D. (author), Henderson, J.E. (author), TNO Kwaliteit van Leven (author)Fibroblast growth factor (FGF) receptor 3 has been identified as a key regulator of endochondral bone development and of post-natal bone metabolism through its action on growth plate chondrocytes and osteoblasts, respectively. It has also been shown to promote chondrogenesis and cartilage production by cultured pre-chondrogenic cells in response...article 2006
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Sivan, S.S. (author), Tsitron, E. (author), Wachtel, E. (author), Roughley, P. (author), Sakkee, N. (author), van der Ham, F. (author), de Groot, J. (author), Maroudas, A. (author), TNO Kwaliteit van Leven (author)During aging and degeneration, many changes occur in the structure and composition of human cartilaginous tissues, which include the accumulation of the AGE (advanced glycation end-product), pentosidine, in long-lived proteins. In the present study, we investigated the accumulation of pentosidine in constituents of the human IVD (intervertebral...article 2006
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van Hinsbergh, V.W.M. (author), Engelse, M.A. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)Pericellular proteases play an important role in angiogenesis and vasculogenesis. They comprise (membrane-type) matrix metalloproteinases [(MT-)MMPs], serine proteases, cysteine cathepsins, and membrane-bound aminopeptidases. Specific inhibitors regulate them. Major roles in initiating angiogenesis have been attributed to MT1-matrix...article 2006