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1. Supplementation of diet with non-digestible oligosaccharides alters the intestinal microbiota, but not arthritis development, in IL-1 receptor antagonist deficient mice

Author

Sub Theoretical Biology & Bioinformatics, Afd Pharmacology, Pharmacology, Rogier, Rebecca, Ederveen, Thomas H A, Wopereis, Harm, Hartog, Anita, Boekhorst, Jos, van Hijum, Sacha A F T, Knol, Jan, Garssen, Johan, Walgreen, Birgitte, Helsen, Monique M, van der Kraan, Peter M, van Lent, Peter L E M, van de Loo, Fons A J, Abdollahi-Roodsaz, Shahla, Koenders, Marije I, Sub Theoretical Biology & Bioinformatics, Afd Pharmacology, Pharmacology, Rogier, Rebecca, Ederveen, Thomas H A, Wopereis, Harm, Hartog, Anita, Boekhorst, Jos, van Hijum, Sacha A F T, Knol, Jan, Garssen, Johan, Walgreen, Birgitte, Helsen, Monique M, van der Kraan, Peter M, van Lent, Peter L E M, van de Loo, Fons A J, Abdollahi-Roodsaz, Shahla, and Koenders, Marije I

Published
2019

2. Supplementation of diet with non-digestible oligosaccharides alters the intestinal microbiota, but not arthritis development, in IL-1 receptor antagonist deficient mice

Author

Sub Theoretical Biology & Bioinformatics, Afd Pharmacology, Pharmacology, Rogier, Rebecca, Ederveen, Thomas H A, Wopereis, Harm, Hartog, Anita, Boekhorst, Jos, van Hijum, Sacha A F T, Knol, Jan, Garssen, Johan, Walgreen, Birgitte, Helsen, Monique M, van der Kraan, Peter M, van Lent, Peter L E M, van de Loo, Fons A J, Abdollahi-Roodsaz, Shahla, Koenders, Marije I, Sub Theoretical Biology & Bioinformatics, Afd Pharmacology, Pharmacology, Rogier, Rebecca, Ederveen, Thomas H A, Wopereis, Harm, Hartog, Anita, Boekhorst, Jos, van Hijum, Sacha A F T, Knol, Jan, Garssen, Johan, Walgreen, Birgitte, Helsen, Monique M, van der Kraan, Peter M, van Lent, Peter L E M, van de Loo, Fons A J, Abdollahi-Roodsaz, Shahla, and Koenders, Marije I

Published
2019

3. Supplementation of diet with non-digestible oligosaccharides alters the intestinal microbiota, but not arthritis development, in IL-1 receptor antagonist deficient mice

Author

Sub Theoretical Biology & Bioinformatics, Afd Pharmacology, Pharmacology, Rogier, Rebecca, Ederveen, Thomas H A, Wopereis, Harm, Hartog, Anita, Boekhorst, Jos, van Hijum, Sacha A F T, Knol, Jan, Garssen, Johan, Walgreen, Birgitte, Helsen, Monique M, van der Kraan, Peter M, van Lent, Peter L E M, van de Loo, Fons A J, Abdollahi-Roodsaz, Shahla, Koenders, Marije I, Sub Theoretical Biology & Bioinformatics, Afd Pharmacology, Pharmacology, Rogier, Rebecca, Ederveen, Thomas H A, Wopereis, Harm, Hartog, Anita, Boekhorst, Jos, van Hijum, Sacha A F T, Knol, Jan, Garssen, Johan, Walgreen, Birgitte, Helsen, Monique M, van der Kraan, Peter M, van Lent, Peter L E M, van de Loo, Fons A J, Abdollahi-Roodsaz, Shahla, and Koenders, Marije I

Published
2019

4. Supplementation of diet with non-digestible oligosaccharides alters the intestinal microbiota, but not arthritis development, in IL-1 receptor antagonist deficient mice

Author

Rogier, Rebecca, Ederveen, Thomas H.A., Wopereis, Harm, Hartog, Anita, Boekhorst, Jos, Van Hijum, Sacha A.F.T., Knol, Jan, Garssen, Johan, Walgreen, Birgitte, Helsen, Monique M., Van Der Kraan, Peter M., Van Lent, Peter L.E.M., Van De Loo, Fons A.J., Abdollahi-Roodsaz, Shahla, Koenders, Marije I., Rogier, Rebecca, Ederveen, Thomas H.A., Wopereis, Harm, Hartog, Anita, Boekhorst, Jos, Van Hijum, Sacha A.F.T., Knol, Jan, Garssen, Johan, Walgreen, Birgitte, Helsen, Monique M., Van Der Kraan, Peter M., Van Lent, Peter L.E.M., Van De Loo, Fons A.J., Abdollahi-Roodsaz, Shahla, and Koenders, Marije I.

Abstract

The intestinal microbiome is perturbed in patients with new-onset and chronic autoimmune inflammatory arthritis. Recent studies in mouse models suggest that development and progression of autoimmune arthritis is highly affected by the intestinal microbiome. This makes modulation of the intestinal microbiota an interesting novel approach to suppress inflammatory arthritis. Prebiotics, defined as non-digestible carbohydrates that selectively stimulate the growth and activity of beneficial microorganisms, provide a relatively non-invasive approach to modulate the intestinal microbiota. The aim of this study was to assess the therapeutic potential of dietary supplementation with a prebiotic mixture of 90% short-chain galacto-oligosaccharides and 10% long-chain fructo-oligosaccharides (scGOS/lcFOS) in experimental arthritis in mice. We here show that dietary supplementation with scGOS/ lcFOS has a pronounced effect on the composition of the fecal microbiota. Interestingly, the genera Enterococcus and Clostridium were markedly decreased by scGOS/lcFOS dietary supplementation. In contrast, the family Lachnospiraceae and the genus Lactobacillus, both associated with healthy microbiota, increased in mice receiving scGOS/lcFOS diet. However, the scGOS/lcFOS induced alterations of the intestinal microbiota did not induce significant effects on the intestinal and systemic T helper cell subsets and were not sufficient to reproducibly suppress arthritis in mice. As expected, we did observe a significant increase in the bone mineral density in mice upon dietary supplementation with scGOS/lcFOS for 8 weeks. Altogether, this study suggests that dietary scGOS/lcFOS supplementation is able to promote presumably healthy gut microbiota and improve bone mineral density, but not inflammation, in arthritis-prone mice.

Published
2019

5. Identification of TGF beta-related genes regulated in murine osteoarthritis and chondrocyte hypertrophy by comparison of multiple microarray datasets

Author

de Kroon, Laurie M. G., van den Akker, Guus G. H., Brachvogel, Bent, Narcisi, Roberto, Belluoccio, Daniele, Jenner, Florien, Bateman, John F., Little, Christopher B., Brama, Pieter A. J., Davidson, Esmeralda N. Blaney, van der Kraan, Peter M., van Osch, Gerjo J. V. M., de Kroon, Laurie M. G., van den Akker, Guus G. H., Brachvogel, Bent, Narcisi, Roberto, Belluoccio, Daniele, Jenner, Florien, Bateman, John F., Little, Christopher B., Brama, Pieter A. J., Davidson, Esmeralda N. Blaney, van der Kraan, Peter M., and van Osch, Gerjo J. V. M.

Abstract

Objective: Osteoarthritis (OA) is a joint disease characterized by progressive degeneration of articular cartilage. Some features of OA, including chondrocyte hypertrophy and focal calcification of articular cartilage, resemble the endochondral ossification processes. Alterations in transforming growth factor beta (TGF beta) signaling have been associated with OA as well as with chondrocyte hypertrophy. Our aim was to identify novel candidate genes implicated in chondrocyte hypertrophy during OA pathogenesis by determining which TGF beta-related genes are regulated during murine OA and endochondral ossification. Methods: A list of 580 TGF beta-related genes, including TGF beta signaling pathway components and TGF beta-target genes, was generated. Regulation of these TGF beta-related genes was assessed in a microarray of murine OA cartilage: 1, 2 and 6 weeks after destabilization of the medial meniscus (DMM). Subsequently, genes regulated in the DMM model were studied in two independent murine microarray datasets on endochondral ossification: the growth plate and transient embryonic cartilage (joint development). Results: A total of 106 TGF beta-related genes were differentially expressed in articular cartilage of DMM-operated mice compared to sham-control. From these genes, 43 were similarly regulated during chondrocyte hypertrophy in the growth plate or embryonic joint development. Among these 43 genes, 18 genes have already been associated with OA. The remaining 25 genes were considered as novel candidate genes involved in OA pathogenesis and endochondral ossification. In supplementary data of published human OA microarrays we found indications that 15 of the 25 novel genes are indeed regulated in articular cartilage of human OA patients. Conclusion: By focusing on TGF beta-related genes during OA and chondrocyte hypertrophy in mice, we identified 18 known and 25 new candidate genes potentially implicated in phenotypical changes in chondrocytes leading to OA. We p

Published
2018

6. Imaging fibroblast activation protein to monitor therapeutic effects of neutralizing interleukin-22 in collagen-induced arthritis

Author

Afd Pharmaceutics, Pharmaceutics, van der Geest, Tessa, Roeleveld, Debbie M, Walgreen, Birgitte, Helsen, Monique M, Nayak, Tapan K, Klein, Christian, Hegen, Martin, Storm, Gert, Metselaar, Josbert M, van den Berg, Wim B, van der Kraan, Peter M, Laverman, Peter, Boerman, Otto C, Koenders, Marije I, Afd Pharmaceutics, Pharmaceutics, van der Geest, Tessa, Roeleveld, Debbie M, Walgreen, Birgitte, Helsen, Monique M, Nayak, Tapan K, Klein, Christian, Hegen, Martin, Storm, Gert, Metselaar, Josbert M, van den Berg, Wim B, van der Kraan, Peter M, Laverman, Peter, Boerman, Otto C, and Koenders, Marije I

Published
2018

7. Imaging fibroblast activation protein to monitor therapeutic effects of neutralizing interleukin-22 in collagen-induced arthritis

Author

Afd Pharmaceutics, Pharmaceutics, van der Geest, Tessa, Roeleveld, Debbie M, Walgreen, Birgitte, Helsen, Monique M, Nayak, Tapan K, Klein, Christian, Hegen, Martin, Storm, Gert, Metselaar, Josbert M, van den Berg, Wim B, van der Kraan, Peter M, Laverman, Peter, Boerman, Otto C, Koenders, Marije I, Afd Pharmaceutics, Pharmaceutics, van der Geest, Tessa, Roeleveld, Debbie M, Walgreen, Birgitte, Helsen, Monique M, Nayak, Tapan K, Klein, Christian, Hegen, Martin, Storm, Gert, Metselaar, Josbert M, van den Berg, Wim B, van der Kraan, Peter M, Laverman, Peter, Boerman, Otto C, and Koenders, Marije I

Published
2018

8. Imaging fibroblast activation protein to monitor therapeutic effects of neutralizing interleukin-22 in collagen-induced arthritis

Author

Afd Pharmaceutics, Pharmaceutics, van der Geest, Tessa, Roeleveld, Debbie M, Walgreen, Birgitte, Helsen, Monique M, Nayak, Tapan K, Klein, Christian, Hegen, Martin, Storm, Gert, Metselaar, Josbert M, van den Berg, Wim B, van der Kraan, Peter M, Laverman, Peter, Boerman, Otto C, Koenders, Marije I, Afd Pharmaceutics, Pharmaceutics, van der Geest, Tessa, Roeleveld, Debbie M, Walgreen, Birgitte, Helsen, Monique M, Nayak, Tapan K, Klein, Christian, Hegen, Martin, Storm, Gert, Metselaar, Josbert M, van den Berg, Wim B, van der Kraan, Peter M, Laverman, Peter, Boerman, Otto C, and Koenders, Marije I

Published
2018

9. Identification of TGF beta-related genes regulated in murine osteoarthritis and chondrocyte hypertrophy by comparison of multiple microarray datasets

Author

de Kroon, Laurie M. G., van den Akker, Guus G. H., Brachvogel, Bent, Narcisi, Roberto, Belluoccio, Daniele, Jenner, Florien, Bateman, John F., Little, Christopher B., Brama, Pieter A. J., Davidson, Esmeralda N. Blaney, van der Kraan, Peter M., van Osch, Gerjo J. V. M., de Kroon, Laurie M. G., van den Akker, Guus G. H., Brachvogel, Bent, Narcisi, Roberto, Belluoccio, Daniele, Jenner, Florien, Bateman, John F., Little, Christopher B., Brama, Pieter A. J., Davidson, Esmeralda N. Blaney, van der Kraan, Peter M., and van Osch, Gerjo J. V. M.

Abstract

Objective: Osteoarthritis (OA) is a joint disease characterized by progressive degeneration of articular cartilage. Some features of OA, including chondrocyte hypertrophy and focal calcification of articular cartilage, resemble the endochondral ossification processes. Alterations in transforming growth factor beta (TGF beta) signaling have been associated with OA as well as with chondrocyte hypertrophy. Our aim was to identify novel candidate genes implicated in chondrocyte hypertrophy during OA pathogenesis by determining which TGF beta-related genes are regulated during murine OA and endochondral ossification. Methods: A list of 580 TGF beta-related genes, including TGF beta signaling pathway components and TGF beta-target genes, was generated. Regulation of these TGF beta-related genes was assessed in a microarray of murine OA cartilage: 1, 2 and 6 weeks after destabilization of the medial meniscus (DMM). Subsequently, genes regulated in the DMM model were studied in two independent murine microarray datasets on endochondral ossification: the growth plate and transient embryonic cartilage (joint development). Results: A total of 106 TGF beta-related genes were differentially expressed in articular cartilage of DMM-operated mice compared to sham-control. From these genes, 43 were similarly regulated during chondrocyte hypertrophy in the growth plate or embryonic joint development. Among these 43 genes, 18 genes have already been associated with OA. The remaining 25 genes were considered as novel candidate genes involved in OA pathogenesis and endochondral ossification. In supplementary data of published human OA microarrays we found indications that 15 of the 25 novel genes are indeed regulated in articular cartilage of human OA patients. Conclusion: By focusing on TGF beta-related genes during OA and chondrocyte hypertrophy in mice, we identified 18 known and 25 new candidate genes potentially implicated in phenotypical changes in chondrocytes leading to OA. We p

Published
2018

10. Induction of Matrix Metalloproteinase Expression by Synovial Wnt Signaling and Association With Disease Progression in Early Symptomatic Osteoarthriti

Author

van den Bosch, Martijn H., Blom, Arjen B, van de Loo, Fons A J, Koenders, Marije I, Lafeber, Floris P., Van Den Berg, Wim B., van der Kraan, Peter M, van Lent, Peter L E M, van den Bosch, Martijn H., Blom, Arjen B, van de Loo, Fons A J, Koenders, Marije I, Lafeber, Floris P., Van Den Berg, Wim B., van der Kraan, Peter M, and van Lent, Peter L E M

Published
2017

11. Induction of Matrix Metalloproteinase Expression by Synovial Wnt Signaling and Association With Disease Progression in Early Symptomatic Osteoarthriti

Author

van den Bosch, Martijn H., Blom, Arjen B, van de Loo, Fons A J, Koenders, Marije I, Lafeber, Floris P., Van Den Berg, Wim B., van der Kraan, Peter M, van Lent, Peter L E M, van den Bosch, Martijn H., Blom, Arjen B, van de Loo, Fons A J, Koenders, Marije I, Lafeber, Floris P., Van Den Berg, Wim B., van der Kraan, Peter M, and van Lent, Peter L E M

Published
2017

12. Aberrant intestinal microbiota due to IL-1 receptor antagonist deficiency promotes IL-17- and TLR4-dependent arthritis

Author

Afd Pharmacology, Pharmacology, Rogier, Rebecca, Ederveen, Thomas H A, Boekhorst, Jos, Wopereis, Harm, Scher, Jose U, Manasson, Julia, Frambach, Sanne J C M, Knol, Jan, Garssen, Johan, van der Kraan, Peter M, Koenders, Marije I., Van Den Berg, Wim B., van Hijum, Sacha A F T, Abdollahi-Roodsaz, Shahla, Afd Pharmacology, Pharmacology, Rogier, Rebecca, Ederveen, Thomas H A, Boekhorst, Jos, Wopereis, Harm, Scher, Jose U, Manasson, Julia, Frambach, Sanne J C M, Knol, Jan, Garssen, Johan, van der Kraan, Peter M, Koenders, Marije I., Van Den Berg, Wim B., van Hijum, Sacha A F T, and Abdollahi-Roodsaz, Shahla

Published
2017

13. Induction of Matrix Metalloproteinase Expression by Synovial Wnt Signaling and Association With Disease Progression in Early Symptomatic Osteoarthriti

Author

van den Bosch, Martijn H., Blom, Arjen B, van de Loo, Fons A J, Koenders, Marije I, Lafeber, Floris P., Van Den Berg, Wim B., van der Kraan, Peter M, van Lent, Peter L E M, van den Bosch, Martijn H., Blom, Arjen B, van de Loo, Fons A J, Koenders, Marije I, Lafeber, Floris P., Van Den Berg, Wim B., van der Kraan, Peter M, and van Lent, Peter L E M

Published
2017

14. Induction of Matrix Metalloproteinase Expression by Synovial Wnt Signaling and Association With Disease Progression in Early Symptomatic Osteoarthriti

Author

AIOS Psychiatrie, UMC Utrecht, Lab Reumatologie/Klinische Immunologie, Regenerative Medicine and Stem Cells, Infection & Immunity, dLAB Biobank, van den Bosch, Martijn H., Blom, Arjen B, van de Loo, Fons A J, Koenders, Marije I, Lafeber, Floris P., Van Den Berg, Wim B., van der Kraan, Peter M, van Lent, Peter L E M, AIOS Psychiatrie, UMC Utrecht, Lab Reumatologie/Klinische Immunologie, Regenerative Medicine and Stem Cells, Infection & Immunity, dLAB Biobank, van den Bosch, Martijn H., Blom, Arjen B, van de Loo, Fons A J, Koenders, Marije I, Lafeber, Floris P., Van Den Berg, Wim B., van der Kraan, Peter M, and van Lent, Peter L E M

Published
2017

15. Aberrant intestinal microbiota due to IL-1 receptor antagonist deficiency promotes IL-17- and TLR4-dependent arthritis

Author

Afd Pharmacology, Pharmacology, Rogier, Rebecca, Ederveen, Thomas H A, Boekhorst, Jos, Wopereis, Harm, Scher, Jose U, Manasson, Julia, Frambach, Sanne J C M, Knol, Jan, Garssen, Johan, van der Kraan, Peter M, Koenders, Marije I., Van Den Berg, Wim B., van Hijum, Sacha A F T, Abdollahi-Roodsaz, Shahla, Afd Pharmacology, Pharmacology, Rogier, Rebecca, Ederveen, Thomas H A, Boekhorst, Jos, Wopereis, Harm, Scher, Jose U, Manasson, Julia, Frambach, Sanne J C M, Knol, Jan, Garssen, Johan, van der Kraan, Peter M, Koenders, Marije I., Van Den Berg, Wim B., van Hijum, Sacha A F T, and Abdollahi-Roodsaz, Shahla

Published
2017

16. Aberrant intestinal microbiota due to IL-1 receptor antagonist deficiency promotes IL-17- and TLR4-dependent arthritis

Author

Rogier, Rebecca, Ederveen, Thomas H.A., Boekhorst, Jos, Wopereis, Harm, Scher, Jose U., Manasson, Julia, Frambach, Sanne J.C.M., Knol, Jan, Garssen, Johan, van der Kraan, Peter M., Koenders, Marije I., van den Berg, Wim B., van Hijum, Sacha A.F.T., Abdollahi-Roodsaz, Shahla, Rogier, Rebecca, Ederveen, Thomas H.A., Boekhorst, Jos, Wopereis, Harm, Scher, Jose U., Manasson, Julia, Frambach, Sanne J.C.M., Knol, Jan, Garssen, Johan, van der Kraan, Peter M., Koenders, Marije I., van den Berg, Wim B., van Hijum, Sacha A.F.T., and Abdollahi-Roodsaz, Shahla

Abstract

BACKGROUND: Perturbation of commensal intestinal microbiota has been associated with several autoimmune diseases. Mice deficient in interleukin-1 receptor antagonist (Il1rn -/- mice) spontaneously develop autoimmune arthritis and are susceptible to other autoimmune diseases such as psoriasis, diabetes, and encephalomyelitis; however, the mechanisms of increased susceptibility to these autoimmune phenotypes are poorly understood. We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) in regulation of commensal intestinal microbiota, and assessed the involvement of microbiota subsets and innate and adaptive mucosal immune responses that underlie the development of spontaneous arthritis in Il1rn -/- mice.RESULTS: Using high-throughput 16S rRNA gene sequencing, we show that IL-1Ra critically maintains the diversity and regulates the composition of intestinal microbiota in mice. IL-1Ra deficiency reduced the intestinal microbial diversity and richness, and caused specific taxonomic alterations characterized by overrepresented Helicobacter and underrepresented Ruminococcus and Prevotella. Notably, the aberrant intestinal microbiota in IL1rn -/- mice specifically potentiated IL-17 production by intestinal lamina propria (LP) lymphocytes and skewed the LP T cell balance in favor of T helper 17 (Th17) cells, an effect transferable to WT mice by fecal microbiota. Importantly, LP Th17 cell expansion and the development of spontaneous autoimmune arthritis in IL1rn -/- mice were attenuated under germ-free condition. Selective antibiotic treatment revealed that tobramycin-induced alterations of commensal intestinal microbiota, i.e., reduced Helicobacter, Flexispira, Clostridium, and Dehalobacterium, suppressed arthritis in IL1rn -/- mice. The arthritis phenotype in IL1rn -/- mice was previously shown to depend on Toll-like receptor 4 (TLR4). Using the ablation of both IL-1Ra and TLR4, we here show that the aberrations in the IL1rn -/- microbiota are partly TLR4-de

Published
2017

17. Translation of clinical problems in osteoarthritis into pathophysiological research goals

Author

Van Der Kraan, Peter M., Berenbaum, Francis, Blanco, Francisco J., De Bari, Cosimo, Lafeber, Floris, Hauge, Ellen, Higginbottom, Adele, Ioan-Facsinay, Andreea, Loughlin, John, Meulenbelt, Ingrid, Moilanen, Eeva, Pitsillidou, Irene, Tsezou, Aspasia, Van Meurs, Joyce, Vincent, Tonia, Wittoek, Ruth, Lories, Rik, Van Der Kraan, Peter M., Berenbaum, Francis, Blanco, Francisco J., De Bari, Cosimo, Lafeber, Floris, Hauge, Ellen, Higginbottom, Adele, Ioan-Facsinay, Andreea, Loughlin, John, Meulenbelt, Ingrid, Moilanen, Eeva, Pitsillidou, Irene, Tsezou, Aspasia, Van Meurs, Joyce, Vincent, Tonia, Wittoek, Ruth, and Lories, Rik

Published
2016

18. Translation of clinical problems in osteoarthritis into pathophysiological research goals

Author

Van Der Kraan, Peter M., Berenbaum, Francis, Blanco, Francisco J., De Bari, Cosimo, Lafeber, Floris, Hauge, Ellen, Higginbottom, Adele, Ioan-Facsinay, Andreea, Loughlin, John, Meulenbelt, Ingrid, Moilanen, Eeva, Pitsillidou, Irene, Tsezou, Aspasia, Van Meurs, Joyce, Vincent, Tonia, Wittoek, Ruth, Lories, Rik, Van Der Kraan, Peter M., Berenbaum, Francis, Blanco, Francisco J., De Bari, Cosimo, Lafeber, Floris, Hauge, Ellen, Higginbottom, Adele, Ioan-Facsinay, Andreea, Loughlin, John, Meulenbelt, Ingrid, Moilanen, Eeva, Pitsillidou, Irene, Tsezou, Aspasia, Van Meurs, Joyce, Vincent, Tonia, Wittoek, Ruth, and Lories, Rik

Published
2016

19. Translation of clinical problems in osteoarthritis into pathophysiological research goals

Author

Van Der Kraan, Peter M., Berenbaum, Francis, Blanco, Francisco J., De Bari, Cosimo, Lafeber, Floris, Hauge, Ellen, Higginbottom, Adele, Ioan-Facsinay, Andreea, Loughlin, John, Meulenbelt, Ingrid, Moilanen, Eeva, Pitsillidou, Irene, Tsezou, Aspasia, Van Meurs, Joyce, Vincent, Tonia, Wittoek, Ruth, Lories, Rik, Van Der Kraan, Peter M., Berenbaum, Francis, Blanco, Francisco J., De Bari, Cosimo, Lafeber, Floris, Hauge, Ellen, Higginbottom, Adele, Ioan-Facsinay, Andreea, Loughlin, John, Meulenbelt, Ingrid, Moilanen, Eeva, Pitsillidou, Irene, Tsezou, Aspasia, Van Meurs, Joyce, Vincent, Tonia, Wittoek, Ruth, and Lories, Rik

Published
2016

20. Translation of clinical problems in osteoarthritis into pathophysiological research goals

Author

Lab Reumatologie/Klinische Immunologie, Regenerative Medicine and Stem Cells, Infection & Immunity, Van Der Kraan, Peter M., Berenbaum, Francis, Blanco, Francisco J., De Bari, Cosimo, Lafeber, Floris, Hauge, Ellen, Higginbottom, Adele, Ioan-Facsinay, Andreea, Loughlin, John, Meulenbelt, Ingrid, Moilanen, Eeva, Pitsillidou, Irene, Tsezou, Aspasia, Van Meurs, Joyce, Vincent, Tonia, Wittoek, Ruth, Lories, Rik, Lab Reumatologie/Klinische Immunologie, Regenerative Medicine and Stem Cells, Infection & Immunity, Van Der Kraan, Peter M., Berenbaum, Francis, Blanco, Francisco J., De Bari, Cosimo, Lafeber, Floris, Hauge, Ellen, Higginbottom, Adele, Ioan-Facsinay, Andreea, Loughlin, John, Meulenbelt, Ingrid, Moilanen, Eeva, Pitsillidou, Irene, Tsezou, Aspasia, Van Meurs, Joyce, Vincent, Tonia, Wittoek, Ruth, and Lories, Rik

Published
2016

21. Translation of clinical problems in osteoarthritis into pathophysiological research goals

Author

van der Kraan, Peter M., Berenbaum, Francis, Blanco García, Francisco J, De Bari, Cosimo, Lafeber, Floris, Hauge, Ellen, Higginbottom, Adele, Ioan-Facsinay, Andreea, Loughlin, John, Meulenbelt, Ingrid, Moilanen, Eeva, Pitsilidou, Irene, Tsezou, Aspasia, van Meurs, Joyce, Vincent, Tonia, Wittoek, Ruth, Lories, Rik, van der Kraan, Peter M., Berenbaum, Francis, Blanco García, Francisco J, De Bari, Cosimo, Lafeber, Floris, Hauge, Ellen, Higginbottom, Adele, Ioan-Facsinay, Andreea, Loughlin, John, Meulenbelt, Ingrid, Moilanen, Eeva, Pitsilidou, Irene, Tsezou, Aspasia, van Meurs, Joyce, Vincent, Tonia, Wittoek, Ruth, and Lories, Rik

Abstract

[Abstract] Osteoarthritis (OA) accounts for more disability among the elderly than any other disease and is associated with an increased mortality rate. The prevalence in Europe will rise in the future since this continent has a strongly ageing population and an obesity epidemic; obesity and age both being major risk factors for OA. No adequate therapeutic options, besides joint replacement, are available, although they are greatly needed and should be acquired by adequate research investments. However, the perspective on OA from a researcher's point of view is not always aligned with the perspective of a patient with OA. Researchers base their views on OA mainly on abnormalities in structure and function while patients consider OA as a collection of symptoms. In this viewpoint paper, we discuss the possibility of translating the most important clinical problems into pathophysiological research goals to facilitate the translation from bench to bedside and vice versa. This viewpoint is the outcome of a dialogue within the ‘European League Against Rheumatism study group on OA’ and People with Arthritis/Rheumatism across Europe (PARE) representatives.

Published
2016

22. A theranostic agent to enhance osteogenic and magnetic resonance imaging properties of calcium phosphate cements

Author

Ventura, Manuela, Ventura, Manuela, Sun, Yi, Cremers, Sjef, Borm, Paul, Birgani, Zeinab T., Habibovic, Pamela, Heerschap, Arend, van der Kraan, Peter M., Jansen, John A., Walboomers, X. Frank, Ventura, Manuela, Ventura, Manuela, Sun, Yi, Cremers, Sjef, Borm, Paul, Birgani, Zeinab T., Habibovic, Pamela, Heerschap, Arend, van der Kraan, Peter M., Jansen, John A., and Walboomers, X. Frank

Abstract

With biomimetic biomaterials, like calcium phosphate cements (CPCs), non-invasive assessment of tissue regeneration is challenging. This study describes a theranostic agent (TA) to simultaneously enhance both imaging and osteogenic properties of such a bone substitute material. For this purpose, mesoporous silica beads were produced containing an iron oxide core to enhance bone magnetic resonance (MR) contrast. The same beads were functionalized with silane linkers to immobilize the osteoinductive protein BMP-2, and finally received a calcium phosphate coating, before being embedded in the CPC. Both in vitro and in vivo tests were performed. In vitro testing showed that the TA beads did not interfere with essential material properties like cement setting. Furthermore, bioactive BMP-2 could be efficiently released from the carrier-beads. In vivo testing in a femoral condyle defect rat model showed long-term MR contrast enhancement, as well as improved osteogenic capacity. Moreover, the TA was released during CPC degradation and was not incorporated into the newly formed bone. In conclusion, the described TA was shown to be suitable for longitudinal material degradation and bone healing studies.

Published
2014

23. A theranostic agent to enhance osteogenic and magnetic resonance imaging properties of calcium phosphate cements

Author

Ventura, Manuela, Sun, Yi, Cremers, Sjef, Borm, Paul, Birgani, Zeinab T., Habibovic, Pamela, Heerschap, Arend, van der Kraan, Peter M., Jansen, John A., Walboomers, X. Frank, Ventura, Manuela, Sun, Yi, Cremers, Sjef, Borm, Paul, Birgani, Zeinab T., Habibovic, Pamela, Heerschap, Arend, van der Kraan, Peter M., Jansen, John A., and Walboomers, X. Frank

Abstract

With biomimetic biomaterials, like calcium phosphate cements (CPCs), non-invasive assessment of tissue regeneration is challenging. This study describes a theranostic agent (TA) to simultaneously enhance both imaging and osteogenic properties of such a bone substitute material. For this purpose, mesoporous silica beads were produced containing an iron oxide core to enhance bone magnetic resonance (MR) contrast. The same beads were functionalized with silane linkers to immobilize the osteoinductive protein BMP-2, and finally received a calcium phosphate coating, before being embedded in the CPC. Both in vitro and in vivo tests were performed. In vitro testing showed that the TA beads did not interfere with essential material properties like cement setting. Furthermore, bioactive BMP-2 could be efficiently released from the carrier-beads. In vivo testing in a femoral condyle defect rat model showed long-term MR contrast enhancement, as well as improved osteogenic capacity. Moreover, the TA was released during CPC degradation and was not incorporated into the newly formed bone. In conclusion, the described TA was shown to be suitable for longitudinal material degradation and bone healing studies.

Published
2014

24. Aberrant intestinal microbiota due to IL-1 receptor antagonist deficiency promotes IL-17- and TLR4-dependent arthritis

Author

Rogier, Rebecca, Ederveen, Thomas H.A., Boekhorst, Jos, Wopereis, H.J., Scher, Jose U., Manasson, Julia, Knol, J., Garssen, Johan, van der Kraan, Peter M., Koenders, Marije I., van den Berg, Wim B., van Hijum, Sacha A.F.T., Abdollahi-Roodsaz, Shahla, Rogier, Rebecca, Ederveen, Thomas H.A., Boekhorst, Jos, Wopereis, H.J., Scher, Jose U., Manasson, Julia, Knol, J., Garssen, Johan, van der Kraan, Peter M., Koenders, Marije I., van den Berg, Wim B., van Hijum, Sacha A.F.T., and Abdollahi-Roodsaz, Shahla

Abstract

The aim of this study was to investigate the role of IL-1 receptor signalling and the involvement of Toll-like receptor (TLR) 2 and TLR4 in defining the intestinal microbiota and the associated mucosal and systemic immune response. Multiplex 454 pyrosequencing of V5 and V6 hyper-variable regions of fecal bacterial 16S rRNA was used to define intestinal microbial communities in BALB/c wild type (WT), IL-1Ra-/- and IL-1Ra/TLR double knock-out (DKO) mice.

Published
2014

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