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158 results on '"Roelofs, Anke J"'

1. Recognition and control of neutrophil extracellular trap formation by MICL

Author

Malamud, Mariano, Whitehead, Lauren, McIntosh, Alasdair, Colella, Fabio, Roelofs, Anke J., Kusakabe, Takato, Dambuza, Ivy M., Phillips-Brookes, Annie, Salazar, Fabián, Perez, Federico, Shoesmith, Romey, Zakrzewski, Przemyslaw, Sey, Emily A., Rodrigues, Cecilia, Morvay, Petruta L., Redelinghuys, Pierre, Bedekovic, Tina, Fernandes, Maria J. G., Almizraq, Ruqayyah, Branch, Donald R., Amulic, Borko, Harvey, Jamie, Stewart, Diane, Yuecel, Raif, Reid, Delyth M., McConnachie, Alex, Pickering, Matthew C., Botto, Marina, Iliev, Iliyan D., McInnes, Iain B., De Bari, Cosimo, Willment, Janet A., and Brown, Gordon D.

Published
2024
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14. Spatial lipidomic profiling of mouse joint tissue demonstrates the essential role of PHOSPHO1 in growth plate homeostasis:Spatially resolving the joint lipidome

Author

Tzvetkov, Jordan, Stephen, Louise A, Dillon, Scott, Milan, Jose Luis, Roelofs, Anke J, De Bari, Cosimo, Farquharson, Colin, Larson, Tony, and Genever, Paul

Subjects
MATRIX MINERALIZATION, STATISTICAL METHODS, BONE MODELING AND REMODELING, DISORDERS OF CALCIUM/PHOSPHATE METABOLISM, GROWTH PLATE
Abstract

Lipids play a crucial role in signaling and metabolism, regulating the development and maintenance of the skeleton. Membrane lipids have been hypothesized to act as intermediates upstream of orphan phosphatase 1 (PHOSPHO1), a major contributor to phosphate generation required for bone mineralization. Here, we spatially resolve the lipid atlas of the healthy mouse knee and demonstrate the effects of PHOSPHO1 ablation on the growth plate lipidome. Lipids spanning 17 subclasses were mapped across the knee joints of healthy juvenile and adult mice using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS), with annotation supported by shotgun lipidomics. Multivariate analysis identified 96 and 80 lipid ions with differential abundances across joint tissues in juvenile and adult mice, respectively. In both ages, marrow was enriched in phospholipid platelet activating factors (PAFs) and related metabolites, cortical bone had a low lipid content, whereas lysophospholipids were strikingly enriched in the growth plate, an active site of mineralization and PHOSPHO1 activity. Spatially-resolved profiling of PHOSPHO1-knockout (KO) mice across the resting, proliferating, and hypertrophic growth plate zones revealed 272, 306, and 296 significantly upregulated, and 155, 220, and 190 significantly downregulated features, respectively, relative to wild-type (WT) controls. Of note, phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, lysophosphatidylethanolamine, and phosphatidylethanolamine derived lipid ions were upregulated in PHOSPHO1-KO versus WT. Our imaging pipeline has established a spatially-resolved lipid signature of joint tissues and has demonstrated that PHOSPHO1 ablation significantly alters the growth plate lipidome, highlighting an essential role of the PHOSPHO1-mediated membrane phospholipid metabolism in lipid and bone homeostasis. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Published
2023
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18. Taxonomy of fibroblasts and progenitors in the synovial joint at single-cell resolution.

Author

Collins, Fraser L., Roelofs, Anke J., Symons, Rebecca A., Kania, Karolina, Campbell, Ewan, Collie-duguid, Elaina S. R., Riemen, Anna H. K., Clark, Susan M., and De Bari, Cosimo

Abstract

Objectives: Fibroblasts in synovium include fibroblast-like synoviocytes (FLS) in the lining and Thy1+ connective-tissue fibroblasts in the sublining. We aimed to investigate their developmental origin and relationship with adult progenitors.Methods: To discriminate between Gdf5-lineage cells deriving from the embryonic joint interzone and other Pdgfrα-expressing fibroblasts and progenitors, adult Gdf5-Cre;Tom;Pdgfrα-H2BGFP mice were used and cartilage injury was induced to activate progenitors. Cells were isolated from knees, fibroblasts and progenitors were sorted by fluorescence-activated cell-sorting based on developmental origin, and analysed by single-cell RNA-sequencing. Flow cytometry and immunohistochemistry were used for validation. Clonal-lineage mapping was performed using Gdf5-Cre;Confetti mice.Results: In steady state, Thy1+ sublining fibroblasts were of mixed ontogeny. In contrast, Thy1-Prg4+ lining fibroblasts predominantly derived from the embryonic joint interzone and included Prg4-expressing progenitors distinct from molecularly defined FLS. Clonal-lineage tracing revealed compartmentalisation of Gdf5-lineage fibroblasts between lining and sublining. Following injury, lining hyperplasia resulted from proliferation and differentiation of Prg4-expressing progenitors, with additional recruitment of non-Gdf5-lineage cells, into FLS. Consistent with this, a second population of proliferating cells, enriched near blood vessels in the sublining, supplied activated multipotent cells predicted to give rise to Thy1+ fibroblasts, and to feed into the FLS differentiation trajectory. Transcriptional programmes regulating fibroblast differentiation trajectories were uncovered, identifying Sox5 and Foxo1 as key FLS transcription factors in mice and humans.Conclusions: Our findings blueprint a cell atlas of mouse synovial fibroblasts and progenitors in healthy and injured knees, and provide novel insights into the cellular and molecular principles governing the organisation and maintenance of adult synovial joints. [ABSTRACT FROM AUTHOR]

Published
2023
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20. Targeting the IL-6–Yap–Snail signalling axis in synovial fibroblasts ameliorates inflammatory arthritis

Author

Symons, Rebecca A, primary, Colella, Fabio, additional, Collins, Fraser L, additional, Rafipay, Alexandra J, additional, Kania, Karolina, additional, McClure, Jessica J, additional, White, Nathan, additional, Cunningham, Iain, additional, Ashraf, Sadaf, additional, Hay, Elizabeth, additional, Mackenzie, Kevin S, additional, Howard, Kenneth A, additional, Riemen, Anna H K, additional, Manzo, Antonio, additional, Clark, Susan M, additional, Roelofs, Anke J, additional, and De Bari, Cosimo, additional

Published
2021
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24. BMP signaling: A significant player and therapeutic target for osteoarthritis

Author

Jaswal, Akrit Pran, primary, Kumar, Bhupendra, additional, Roelofs, Anke J., additional, Iqbal, Sayeda Fauzia, additional, Singh, Amaresh Kumar, additional, Riemen, Anna H.K., additional, Wang, Hui, additional, Ashraf, Sadaf, additional, Nanasaheb, Sanap Vaibhav, additional, Agnihotri, Nitin, additional, De Bari, Cosimo, additional, and Bandyopadhyay, Amitabha, additional

Published
2021
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27. Bisphosphonates

Author

Roelofs, Anke J., primary, Ebetino, Frank H., additional, Reszka, Alfred A., additional, Russell, R. Graham G., additional, and Rogers, Michael J., additional

Published
2008
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28. Identification of the skeletal progenitor cells forming osteophytes in osteoarthritis

Author

Roelofs, Anke J, primary, Kania, Karolina, additional, Rafipay, Alexandra J, additional, Sambale, Meike, additional, Kuwahara, Stephanie T, additional, Collins, Fraser L, additional, Smeeton, Joanna, additional, Serowoky, Maxwell A, additional, Rowley, Lynn, additional, Wang, Hui, additional, Gronewold, René, additional, Kapeni, Chrysa, additional, Méndez-Ferrer, Simón, additional, Little, Christopher B, additional, Bateman, John F, additional, Pap, Thomas, additional, Mariani, Francesca V, additional, Sherwood, Joanna, additional, Crump, J Gage, additional, and De Bari, Cosimo, additional

Published
2020
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29. Agrin induces long-term osteochondral regeneration by supporting repair morphogenesis

Author

Eldridge, Suzanne E., primary, Barawi, Aida, additional, Wang, Hui, additional, Roelofs, Anke J., additional, Kaneva, Magdalena, additional, Guan, Zeyu, additional, Lydon, Helen, additional, Thomas, Bethan L., additional, Thorup, Anne-Sophie, additional, Fernandez, Beatriz F., additional, Caxaria, Sara, additional, Strachan, Danielle, additional, Ali, Ahmed, additional, Shanmuganathan, Kanatheepan, additional, Pitzalis, Costantino, additional, Whiteford, James R., additional, Henson, Frances, additional, McCaskie, Andrew W., additional, De Bari, Cosimo, additional, and Dell’Accio, Francesco, additional

Published
2020
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35. Targeting the IL-6-Yap-Snail signalling axis in synovial fibroblasts ameliorates inflammatory arthritis.

Author

Symons, Rebecca A., Colella, Fabio, Collins, Fraser L., Rafipay, Alexandra J., Kania, Karolina, McClure, Jessica J., White, Nathan, Cunningham, Iain, Ashraf, Sadaf, Hay, Elizabeth, Mackenzie, Kevin S., Howard, Kenneth A., Riemen, Anna H. K., Manzo, Antonio, Clark, Susan M., Roelofs, Anke J., Bari, Cosimo De, and De Bari, Cosimo

Abstract

Objective: We aimed to understand the role of the transcriptional co-factor Yes-associated protein (Yap) in the molecular pathway underpinning the pathogenic transformation of synovial fibroblasts (SF) in rheumatoid arthritis (RA) to become invasive and cause joint destruction.Methods: Synovium from patients with RA and mice with antigen-induced arthritis (AIA) was analysed by immunostaining and qRT-PCR. SF were targeted using Pdgfrα-CreER and Gdf5-Cre mice, crossed with fluorescent reporters for cell tracing and Yap-flox mice for conditional Yap ablation. Fibroblast phenotypes were analysed by flow cytometry, and arthritis severity was assessed by histology. Yap activation was detected using Yap-Tead reporter cells and Yap-Snail interaction by proximity ligation assay. SF invasiveness was analysed using matrigel-coated transwells.Results: Yap, its binding partner Snail and downstream target connective tissue growth factor were upregulated in hyperplastic human RA and in mouse AIA synovium, with Yap detected in SF but not macrophages. Lineage tracing showed polyclonal expansion of Pdgfrα-expressing SF during AIA, with predominant expansion of the Gdf5-lineage SF subpopulation descending from the embryonic joint interzone. Gdf5-lineage SF showed increased expression of Yap and adopted an erosive phenotype (podoplanin+Thy-1 cell surface antigen-), invading cartilage and bone. Conditional ablation of Yap in Gdf5-lineage cells or Pdgfrα-expressing fibroblasts ameliorated AIA. Interleukin (IL)-6, but not tumour necrosis factor alpha (TNF-α) or IL-1β, Jak-dependently activated Yap and induced Yap-Snail interaction. SF invasiveness induced by IL-6 stimulation or Snail overexpression was prevented by Yap knockdown, showing a critical role for Yap in SF transformation in RA.Conclusions: Our findings uncover the IL-6-Yap-Snail signalling axis in pathogenic SF in inflammatory arthritis. [ABSTRACT FROM AUTHOR]

Published
2022
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38. Yes-associated protein (YAP) is a negative regulator of chondrogenesis in mesenchymal stem cells

Author

Karystinou, Alexandra, Roelofs, Anke J, Neve, Anna, Cantatore, Francesco P, Wackerhage, Henning, and De Bari, Cosimo

Subjects
Reverse Transcriptase Polymerase Chain Reaction, Immunology, Blotting, Western, Cell Differentiation, Mesenchymal Stem Cells, YAP-Signaling Proteins, Phosphoproteins, Immunohistochemistry, Mice, Inbred C57BL, Mice, Rheumatology, embryonic structures, Immunology and Allergy, Animals, Humans, Chondrogenesis, Cells, Cultured, Research Article, Adaptor Proteins, Signal Transducing, Transcription Factors
Abstract

Introduction The control of differentiation of mesenchymal stromal/stem cells (MSCs) is crucial for tissue engineering strategies employing MSCs. The purpose of this study was to investigate whether the transcriptional co-factor Yes-associated protein (YAP) regulates chondrogenic differentiation of MSCs. Methods Expression of total YAP, its paralogue transcriptional co-activator with PDZ-binding motif (TAZ), and individual YAP transcript variants during in vitro chondrogenesis of human MSCs was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). YAP expression was confirmed by western blotting. To determine the effect of high YAP activity on chondrogenesis, C3H10T1/2 MSC-like cells were transduced with human (h)YAP and treated in micromass with bone morphogenetic protein-2 (BMP-2). Chondrogenic differentiation was assessed by alcian blue staining and expression of chondrocyte-lineage genes. BMP signalling was determined by detection of pSmad1,5,8 by western blotting and expression of BMP target genes by quantitative RT-PCR. Finally, YAP and pYAP were detected in mouse embryo hindlimbs by immunohistochemistry. Results YAP, but not TAZ, was downregulated during in vitro chondrogenesis of human MSCs. One of the YAP transcript variants, however, was upregulated in high-density micromass culture. Overexpression of hYAP in murine C3H10T1/2 MSCs inhibited chondrogenic differentiation. High YAP activity in these cells decreased Smad1,5,8 phosphorylation and expression of the BMP target genes Inhibitor of DNA binding/differentiation (Id)1, Id2 and Id3 in response to BMP-2. In developing mouse limbs, Yap was nuclear in the perichondrium while mostly phosphorylated and cytosolic in cells of the cartilage anlage, suggesting downregulation of Yap co-transcriptional activity during physiological chondrogenesis in vivo. Conclusions Our findings indicate that YAP is a negative regulator of chondrogenic differentiation of MSCs. Downregulation of YAP is required for chondrogenesis through derepression of chondrogenic signalling. Therapeutic targeting of YAP to promote cartilage repair and prevent secondary osteoarthritis is an exciting prospect in rheumatology. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0639-9) contains supplementary material, which is available to authorized users.

Published
2015

40. Fluorescent Bisphosphonate and Carboxyphosphonate Probes: A Versatile Imaging Toolkit for Applications in Bone Biology and Biomedicine

Author

Sun, Shuting, primary, Błażewska, Katarzyna M., additional, Kadina, Anastasia P., additional, Kashemirov, Boris A., additional, Duan, Xuchen, additional, Triffitt, James T., additional, Dunford, James E., additional, Russell, R. Graham G., additional, Ebetino, Frank H., additional, Roelofs, Anke J., additional, Coxon, Fraser P., additional, Lundy, Mark W., additional, and McKenna, Charles E., additional

Published
2015
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43. Influence of bone affinity on the skeletal distribution of fluorescently labeled bisphosphonates in vivo

Author

Roelofs, Anke J, primary, Stewart, Charlotte A, additional, Sun, Shuting, additional, Błażewska, Katarzyna M, additional, Kashemirov, Boris A, additional, McKenna, Charles E, additional, Russell, R Graham G, additional, Rogers, Michael J, additional, Lundy, Mark W, additional, Ebetino, Frank H, additional, and Coxon, Fraser P, additional

Published
2012
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46. Fluorescent risedronate analogues reveal bisphosphonate uptake by bone marrow monocytes and localization around osteocytes in vivo

Author

Roelofs, Anke J, primary, Coxon, Fraser P, additional, Ebetino, Frank H, additional, Lundy, Mark W, additional, Henneman, Zachary J, additional, Nancollas, George H, additional, Sun, Shuting, additional, Blazewska, Katarzyna M, additional, Bala, Joy Lynn F, additional, Kashemirov, Boris A, additional, Khalid, Aysha B, additional, McKenna, Charles E, additional, and Rogers, Michael J, additional

Published
2010
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