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8. Osteogenic Differentiation of Human Gingival Fibroblasts Inhibits Osteoclast Formation.

Author

Ceylan, Merve, Schoenmaker, Ton, Hogervorst, Jolanda M. A., Jansen, Ineke D. C., Schimmel, Irene M., Prins, Caya M., Laine, Marja L., and de Vries, Teun J.

Subjects
*MONONUCLEAR leukocytes, *ENZYME-linked immunosorbent assay, *CELL differentiation, *FIBROBLASTS, *SCANNING electron microscopy, *BONE resorption
Abstract

Gingival fibroblasts (GFs) can differentiate into osteoblast-like cells and induce osteoclast precursors to differentiate into osteoclasts. As it is unclear whether these two processes influence each other, we investigated how osteogenic differentiation of GFs affects their osteoclast-inducing capacity. To establish step-wise mineralization, GFs were cultured in four groups for 3 weeks, without or with osteogenic medium for the final 1, 2, or all 3 weeks. The mineralization was assessed by ALP activity, calcium concentration, scanning electron microscopy (SEM), Alizarin Red staining, and quantitative PCR (qPCR). To induce osteoclast differentiation, these cultures were then co-cultured for a further 3 weeks with peripheral blood mononuclear cells (PBMCs) containing osteoclast precursors. Osteoclast formation was assessed at different timepoints with qPCR, enzyme-linked immunosorbent assay (ELISA), TRAcP activity, and staining. ALP activity and calcium concentration increased significantly over time. As confirmed with the Alizarin Red staining, SEM images showed that the mineralization process occurred over time. Osteoclast numbers decreased in the GF cultures that had undergone osteogenesis. TNF-α secretion, a costimulatory molecule for osteoclast differentiation, was highest in the control group. GFs can differentiate into osteoblast-like cells and their degree of differentiation reduces their osteoclast-inducing capacity, indicating that, with appropriate stimulation, GFs could be used in regenerative periodontal treatments. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Circumstellar C2, CN, and CH+ in the optical spectra of post-AGB stars

Author

Bakker, Eric J., van Dishoeck, Ewine F., Waters, L. B. F. M., and Schoenmaker, Ton

Subjects
Astrophysics
Abstract

We present optical high-resolution spectra of a sample of sixteen post-AGB stars and IRC +10216. Of the post-AGB stars, ten show C2 Phillips and Swan and CN Red System absorption, one CH+ emission, one CH+ absorption, and four without any molecules. We find typically Trot=43-399, 155-202, and 18-50 K, log N = 14.90-15.57, 14.35, and 15.03-16.47 cm-2 for C2, CH+, and CN respectively, and 0.620. The presence of C2 and CN absorption is correlated with cold dust (Tdust<300K) and the presence of CH+ with hot dust (Tdust>300K). All objects with the unidentified 21mum emission feature exhibit C2 and CN absorption, but not all objects with C2 and CN detections exhibit a 21mum feature. The derived expansion velocity, ranging from 5 to 44 km/s, is the same as that derived from CO millimeter line emission. This unambiguously proves that these lines are of circumstellar origin and are formed in the AGB ejecta (circumstellar shell expelled during the preceding AGB phase). Furthermore there seems to be a relation between the C2 molecular column density and the expansion velocity, which is attributed to the fact that a higher carbon abundance of the dust leads to a more efficient acceleration of the AGB wind. Using simple assumptions for the location of the molecular lines and molecular abundances, mass-loss rates have been derived from the molecular absorption lines and are comparable to those obtained from CO emission lines and the infrared excess., Comment: 31 pages, 10 figures, accepted by A&A main journal

Published
1996

11. Circumstellar molecular line absorption and emission in the optical spectra of post-AGB stars

Author

Bakker, Eric J., Lamers, Henny J. G. L. M., Waters, L. B. F. M., and Schoenmaker, Ton

Subjects
Astrophysics
Abstract

We present a list of post-AGB stars showing molecular line absorption and emission in the optical spectrum. Two objects show CH+, one in emission and one in absorption, and ten stars show C2 and CN in absorption. The Doppler velocities of the C2 lines and the rotational temperatures indicate that the line forming region is the AGB remnant. An analysis of the post-AGB stars of which CO millimeter data is available suggests that the C2} expansion velocity is of the same order as the CO expansion velocity. HD56126 has been studied in detail and we find a mass-loss rate of Mdot=2.8e-4 Msol/yr, fC2=2.4e-8 and fCN=1.3e-8. The mass loss derived from C2 is significantly larger than Mdot=1.2e-5 Msol/yr derived from CO. We find that all objects with the 21mu feature in emission show C2 and CN absorption, but not all objects with C2 and CN detections show a 21mu feature., Comment: plain latex 8 pages, 4 postscript figures, uses psfig.sty

Published
1995
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20. Gene Therapy for Fibrodysplasia Ossificans Progressiva: Feasibility and Obstacles

Author

Eekhoff, Elisabeth M.W., primary, de Ruiter, Ruben D., additional, Smilde, Bernard J., additional, Schoenmaker, Ton, additional, de Vries, Teun J., additional, Netelenbos, Coen, additional, Hsiao, Edward C., additional, Scott, Christiaan, additional, Haga, Nobuhiko, additional, Grunwald, Zvi, additional, De Cunto, Carmen L., additional, di Rocco, Maja, additional, Delai, Patricia L. R., additional, Diecidue, Robert J., additional, Madhuri, Vrisha, additional, Cho, Tae-Joon, additional, Morhart, Rolf, additional, Friedman, Clive S., additional, Zasloff, Michael, additional, Pals, Gerard, additional, Shim, Jae-Hyuck, additional, Gao, Guangping, additional, Kaplan, Frederick, additional, Pignolo, Robert J., additional, and Micha, Dimitra, additional

Published
2022
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23. Detection of the mosaic pattern of Post-Zygotic activating GNAS Mutation in a patient with Fibrous Dysplasia

Author

Langstraat, Jorien, Schoenmaker, Ton, Van Essen, Huib W., Zhang, Chen, Wolvius, Eppo B., Eekhoff, Elisabeth M. W., Bravenboer, Nathalie, Helder, Marco N., Oral and Maxillofacial Surgery / Oral Pathology, Clinical chemistry, Internal medicine, AMS - Musculoskeletal Health, AMS - Tissue Function & Regeneration, Amsterdam Gastroenterology Endocrinology Metabolism, and AMS - Ageing & Vitality

Published
2022

24. Intra-pulpal connective tissue formation and the advanced carious lesion:Is chondrogenesis and heterotopic ossification a response to pulpal inflammation?

Author

Demant, Sune, Schoenmaker, Ton, van Erck, Sophie M. G., Dabelsteen, Sally, de Vries, Teun J., Bjørndal, Lars, Demant, Sune, Schoenmaker, Ton, van Erck, Sophie M. G., Dabelsteen, Sally, de Vries, Teun J., and Bjørndal, Lars

Abstract

Aims (a) The aim of this study was to investigate both the formation of dense connective tissue within the dental pulp, and its association with pulpal inflammation in teeth with advanced carious lesions; and (b) to investigate in vitro whether inflammation affects the expression of markers related to chondrogenesis/osteogenesis in pulp cells. Materials and methods Radiology and Histology: Forty-six teeth with advanced carious lesions were radiographically investigated for intra-pulpal radiodense structures. Specimens were processed for histology and stained with haematoxylin/eosin and proteoglycan-specific stains. The intra-pulpal connective tissue was scored as pulp stones or ectopic connective tissue. Cell culture: pulpal cells from human third molars (n = 5) were cultured in chondrogenic medium +/- TLR2/4 agonists. Expression of the genes IL6, TLR2/4, SOX9, COL1A1, COL2A1, TGFB1, RUNX2 and ALPL was assessed by qPCR. Proteoglycan content within cultures was assessed spectrophotometrically. Results Radiodense structures were discovered in about half of all pulps. They were associated with ectopic connective tissue (chi(2) = 8.932, p = .004, OR = 6.80, 95% CI: [1.84, 25.19]) and with pulp stones (chi(2) = 12.274, df = 1, p < .001, OR = 22.167, 95% CI: [2.57, 200.00]). The morphology of the ectopic tissue resembled cartilage and was associated with inflammatory infiltration of the pulp (chi(2) = 10.148, p = .002, OR = 17.77, 95% CI: [2.05, 154.21]). After continuous stimulation of cultured cells with TLR2/4 agonists, the expression of two inflammatory markers increased: IL6 at Days 7 (p = .020) and 14 (p = .008); TLR2 at Days 7 (p = .023) and 14 (p = .009). Similarly, expression of chondrogenic markers decreased: SOX9 at Day 14 (p = .035) and TGFB1 at Day 7 (p = .004), and the osteogenic marker COL1A1 at Day 7 (p = .007). Proteoglycan content did not differ between unstimulated and stimulated cells. Conclusions Ectopic connective tissue resembling cartilage ca

Published
2022

25. Gene Therapy for Fibrodysplasia Ossificans Progressiva: Feasibility and Obstacles

Author

Eekhoff, Elisabeth M W, de Ruiter, Ruben D, Smilde, Bernard J, Schoenmaker, Ton, de Vries, Teun J, Netelenbos, Coen, Hsiao, Edward C, Scott, Christiaan, Haga, Nobuhiko, Grunwald, Zvi, De Cunto, Carmen L, di Rocco, Maja, Delai, Patricia L R, Diecidue, Robert J, Madhuri, Vrisha, Cho, Tae-Joon, Morhart, Rolf, Friedman, Clive S, Zasloff, Michael, Pals, Gerard, Shim, Jae-Hyuck, Gao, Guangping, Kaplan, Frederick, Pignolo, Robert J, Micha, Dimitra, Eekhoff, Elisabeth M W, de Ruiter, Ruben D, Smilde, Bernard J, Schoenmaker, Ton, de Vries, Teun J, Netelenbos, Coen, Hsiao, Edward C, Scott, Christiaan, Haga, Nobuhiko, Grunwald, Zvi, De Cunto, Carmen L, di Rocco, Maja, Delai, Patricia L R, Diecidue, Robert J, Madhuri, Vrisha, Cho, Tae-Joon, Morhart, Rolf, Friedman, Clive S, Zasloff, Michael, Pals, Gerard, Shim, Jae-Hyuck, Gao, Guangping, Kaplan, Frederick, Pignolo, Robert J, and Micha, Dimitra

Abstract

Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease, in which soft connective tissue is converted into heterotopic bone through an endochondral ossification process. Patients succumb early as they gradually become trapped in a second skeleton of heterotopic bone. Although the underlying genetic defect is long known, the inherent complexity of the disease has hindered the discovery of effective preventions and treatments. New developments in the gene therapy field have motivated its consideration as an attractive therapeutic option for FOP. However, the immune system's role in FOP activation and the as-yet unknown primary causative cell, are crucial issues which must be taken into account in the therapy design. While gene therapy offers a potential therapeutic solution, more knowledge about FOP is needed to enable its optimal and safe application.

Published
2022

27. Mutation in the CCAL1 locus accounts for bidirectional process of human subchondral bone turnover and cartilage mineralization

Author

Rodríguez Ruiz, Alejandro, primary, van Hoolwerff, Marcella, additional, Sprangers, Sara, additional, Suchiman, Eka, additional, Schoenmaker, Ton, additional, Dibbets-Schneider, Petra, additional, Bloem, Johan L, additional, Nelissen, Rob G H H, additional, Freund, Christian, additional, Mummery, Christine, additional, Everts, Vincent, additional, de Vries, Teun J, additional, Ramos, Yolande F M, additional, and Meulenbelt, Ingrid, additional

Published
2022
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30. Fibrodysplasia Ossificans Progressiva: What Have We Achieved and Where Are We Now? Follow-up to the 2015 Lorentz Workshop

Author

de Ruiter, Ruben D., primary, Smilde, Bernard J., additional, Pals, Gerard, additional, Bravenboer, Nathalie, additional, Knaus, Petra, additional, Schoenmaker, Ton, additional, Botman, Esmée, additional, Sánchez-Duffhues, Gonzalo, additional, Pacifici, Maurizio, additional, Pignolo, Robert J., additional, Shore, Eileen M., additional, van Egmond, Marjolein, additional, Van Oosterwyck, Hans, additional, Kaplan, Frederick S., additional, Hsiao, Edward C., additional, Yu, Paul B., additional, Bocciardi, Renata, additional, De Cunto, Carmen Laura, additional, Longo Ribeiro Delai, Patricia, additional, de Vries, Teun J., additional, Hilderbrandt, Susanne, additional, Jaspers, Richard T., additional, Keen, Richard, additional, Koolwijk, Peter, additional, Morhart, Rolf, additional, Netelenbos, Jan C., additional, Rustemeyer, Thomas, additional, Scott, Christiaan, additional, Stockklausner, Clemens, additional, ten Dijke, Peter, additional, Triffit, James, additional, Ventura, Francesc, additional, Ravazzolo, Roberto, additional, Micha, Dimitra, additional, and Eekhoff, Elisabeth M. W., additional

Published
2021
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32. Mutation in the CCAL1 locus accounts for bidirectional process of human subchondral bone turnover and cartilage mineralization.

Author

Ruiz, Alejandro Rodríguez, Hoolwerff, Marcella van, Sprangers, Sara, Suchiman, Eka, Schoenmaker, Ton, Dibbets-Schneider, Petra, Bloem, Johan L, Nelissen, Rob G H H, Freund, Christian, Mummery, Christine, Everts, Vincent, Vries, Teun J de, Ramos, Yolande F M, and Meulenbelt, Ingrid

Subjects
CARTILAGE, GENETIC mutation, PHOTON absorptiometry, CELL receptors, MAGNETIC resonance imaging, CHONDROCALCINOSIS, GENE expression, OSTEOARTHRITIS, BONE remodeling, AMINO acids, MONOCYTES, PHENOTYPES
Abstract

Objectives To study the mechanism by which the readthrough mutation in TNFRSF11B , encoding osteoprotegerin (OPG) with additional 19 amino acids at its C-terminus (OPG-XL), causes the characteristic bidirectional phenotype of subchondral bone turnover accompanied by cartilage mineralization in chondrocalcinosis patients. Methods OPG-XL was studied by human induced pluripotent stem cells expressing OPG-XL and two isogenic CRISPR/Cas9-corrected controls in cartilage and bone organoids. Osteoclastogenesis was studied with monocytes from OPG-XL carriers and matched healthy controls followed by gene expression characterization. Dual energy X-ray absorptiometry scans and MRI analyses were used to characterize the phenotype of carriers and non-carriers of the mutation. Results Human OPG-XL carriers relative to sex- and age-matched controls showed, after an initial delay, large active osteoclasts with high number of nuclei. By employing hiPSCs expressing OPG-XL and isogenic CRISPR/Cas9-corrected controls to established cartilage and bone organoids, we demonstrated that expression of OPG-XL resulted in excessive fibrosis in cartilage and high mineralization in bone accompanied by marked downregulation of MGP , encoding matrix Gla protein, and upregulation of DIO2 , encoding type 2 deiodinase, gene expression, respectively. Conclusions The readthrough mutation at CCAL1 locus in TNFRSF11B identifies an unknown role for OPG-XL in subchondral bone turnover and cartilage mineralization in humans via DIO2 and MGP functions. Previously, OPG-XL was shown to affect binding between RANKL and heparan sulphate (HS) resulting in loss of immobilized OPG-XL. Therefore, effects may be triggered by deficiency in the immobilization of OPG-XL Since the characteristic bidirectional pathophysiology of articular cartilage calcification accompanied by low subchondral bone mineralization is also a hallmark of OA pathophysiology, our results are likely extrapolated to common arthropathies. [ABSTRACT FROM AUTHOR]

Published
2023
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39. Activin-A Induces Early Differential Gene Expression Exclusively in Periodontal Ligament Fibroblasts from Fibrodysplasia Ossificans Progressiva Patients

Author

CDL Onderzoek Pasterkamp, Schoenmaker, Ton, Mokry, Michal, Micha, Dimitra, Netelenbos, Coen, Bravenboer, Nathalie, Gilijamse, Marjolijn, Eekhoff, E Marelise W, de Vries, Teun J, CDL Onderzoek Pasterkamp, Schoenmaker, Ton, Mokry, Michal, Micha, Dimitra, Netelenbos, Coen, Bravenboer, Nathalie, Gilijamse, Marjolijn, Eekhoff, E Marelise W, and de Vries, Teun J

Published
2021

41. The epithelial [Ca.sup.2+] channel TRPV5 is essential for proper osteoclastic bone resorption

Author

van der Eerden, Bram C.J., Hoenderop, Joost G.J., de Vries, Teun J., Schoenmaker, Ton, Buurman, Cok J., Uitterlinden, Andre G., Pols, Huibert A.P., Bindels, Rene J.M., and van Leeuwen, Johannes P.T.M.

Subjects
Bones -- Research, Osteoblasts -- Research, Science and technology
Abstract

Bone remodeling involves the interplay of bone resorption and formation and is accurately controlled to maintain bone mass. Both processes require transcellular [Ca.sup.2+] transport, but the molecular mechanisms engaged remain largely elusive. The epithelial [Ca.sup.2+] channel TRPV5 is one of the most [Ca.sup.2+]-selective transient receptor potential (TRP) channels. In this study, the functional role of TRPV5 in bone was investigated. TRPV5 mRNA was expressed in human and murine bone samples and in osteoclasts along with other genes involved in transcellular [Ca.sup.2+] transport, including calbindin[D.sub.9K] and calbindin-[D.sub.28K], [Na.sup.+]/[Ca.sup.2+] exchanger 1, and plasma membrane [Ca.sup.2+]-ATPase 1b. TRPV5 expression in murine osteoclasts was confirmed by immunostaining and showed predominant localization to the ruffled border membrane. However, TRPV5 was absent in osteoblasts. Analyses of femoral bone sections from TRPV5 knockout (TRPV[5.sup.-/-]) mice revealed increased osteoclast numbers and osteoclast area, whereas the urinary bone resorption marker deoxypyridinoline was reduced compared with WT (TRPV[5.sup.+/+]) mice. In an in vitro bone marrow culture system, the amount of osteoclasts and number of nuclei per osteoclast were significantly elevated in TRPV[5.sup.-/-] compared with TRPV[5.sup.+/+] mice. However, using a functional resorption pit assay, we found that bone resorption was nearly absent in osteoclast cultures from TRP[V.sup.5-/-] mice, supporting the impaired resorption observed in vivo. In conclusion, TRPV5 deficiency leads to an increase in osteoclast size and number, in which [Ca.sup.2+] resorption is nonfunctional. This report identifies TRPV5 as an epithelial [Ca.sup.2+] channel that is essential for osteoclastic bone resorption and demonstrates the significance of transcellular [Ca.sup.2+] transport in osteoclastic function. tartrate-resistant acid phosphatase | 1,25[(OH).sub.2][D.sub.3] | osteoblast | Coomassie blue | laser scanning confocal microscopy

Published
2005

45. Collaboration Around Rare Bone Diseases Leads to the Unique Organizational Incentive of the Amsterdam Bone Center

Author

Eekhoff, Elisabeth M. W., primary, Micha, Dimitra, additional, Forouzanfar, Tymour, additional, de Vries, Teun J., additional, Netelenbos, J. Coen, additional, Klein-Nulend, Jenneke, additional, van Loon, Jack J. W. A., additional, Lubbers, Wouter D., additional, Schwarte, Lothar, additional, Schober, Patrick, additional, Raijmakers, Pieter G. H. M., additional, Teunissen, Bernd P., additional, de Graaf, Pim, additional, Lammertsma, Adriaan A., additional, Yaqub, Maqsood M., additional, Botman, Esmée, additional, Treurniet, Sanne, additional, Smilde, Bernard J., additional, Bökenkamp, Arend, additional, Boonstra, Anco, additional, Kamp, Otto, additional, Nieuwenhuijzen, Jakko A., additional, Visser, Marieke C., additional, Baayen, Hans J. C., additional, Dahele, Max, additional, Eeckhout, Guus A. M., additional, Goderie, Thadé P. M., additional, Smits, Cas, additional, Gilijamse, Marjolijn, additional, Karagozoglu, K. Hakki, additional, van de Valk, Paul, additional, Dickhoff, Chris, additional, Moll, Annette C., additional, Verbraak, Frank F. D., additional, Curro-Tafili, Katie K. R., additional, Ghyczy, Ebba A. E., additional, Rustemeyer, Thomas, additional, Saeed, Peeroz, additional, Maugeri, Alessandra, additional, Pals, Gerard, additional, Ridwan-Pramana, Angela, additional, Pekel, Esther, additional, Schoenmaker, Ton, additional, Lems, Willem, additional, Winters, Henri A. H., additional, Botman, Matthijs, additional, Giannakópoulos, Georgios F., additional, Koolwijk, Peter, additional, Janssen, Jeroen J. W. M., additional, Kloen, Peter, additional, Bravenboer, Nathalie, additional, Smit, Jan Maerten, additional, and Helder, Marco N., additional

Published
2020
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46. Chronic Exposure of Gingival Fibroblasts to TLR2 or TLR4 Agonist Inhibits Osteoclastogenesis but Does Not Affect Osteogenesis

Author

Karlis, Gerasimos D., primary, Schöningh, Emily, additional, Jansen, Ineke D. C., additional, Schoenmaker, Ton, additional, Hogervorst, Jolanda M. A., additional, van Veen, Henk A., additional, Moonen, Carolyn G. J., additional, Łagosz-Ćwik, Katarzyna B., additional, Forouzanfar, Tim, additional, and de Vries, Teun J., additional

Published
2020
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49. Diagnostic Value of Magnetic Resonance Imaging in Fibrodysplasia Ossificans Progressiva

Author

Botman, Esmée, primary, Teunissen, Bernd P, additional, Raijmakers, Pieter, additional, Graaf, Pim, additional, Yaqub, Maqsood, additional, Treurniet, Sanne, additional, Schoenmaker, Ton, additional, Bravenboer, Nathalie, additional, Micha, Dimitra, additional, Pals, Gerard, additional, Bökenkamp, Arend, additional, Netelenbos, J Coen, additional, Lammertsma, Adriaan A, additional, and Eekhoff, Elisabeth MW, additional

Published
2020
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