Deutsch
Löhning lab
We aim to biologically regenerate cartilage by selection and reprogramming of chondrocytes
Pitzer Laboratory of Osteoarthritis Research
The Pitzer Laboratory of Osteoarthritis Research investigates the cellular and molecular mechanisms leading to the development of osteoarthritis (OA). OA is the most frequently occurring joint disease among adults worldwide, it leads to progressive cartilage loss and is often accompanied by inflammatory processes. Recent studies indicate dysfunctional molecular signaling within the cartilage-producing cells of the joints, the chondrocytes. So far, the chondrocytes’ in situ biology is not well understood.
Chondrocytes reside in the joint cartilage layers in different arrangements and with varying types of metabolism. It is not clear yet whether this points to a homogenous population or to differentiated subtypes. Using a 3D-culture system of human chondrocytes that simulates a hypoxic environment, we could show that the activation of specific immune-related receptors leads to impaired cartilage production and altered metabolic activity. Now we investigate a possible connection to the development or progression of OA. Here, our group’s accumulated knowledge on the (re-) programming of T cell subtypes will be transferred to chondrocytes and the field of OA research.
Since we consider the joint as a functional unit, we also analyse the cells building up the bone mass and vascular system. In addition, we examine the infrapatellar fat pad, synovial tissue, and synovial fluid of the material from primary human donors we receive from our colleagues at the Center for Musculoskeletal Surgery of the Charité. After assessing the active genes in specific cell subtypes, we identified a candidate gene that could prove to be important for the therapy of painful ossification processes and osteophyte formation in OA.
In previous studies, we identified central cytokines and key transcription factors controlling the differentiation of T cells into subtypes (Bonilla et al., Science 2012; Peine et al., PLoS Biol. 2013; Baumann et al., PNAS 2015; Peine et al., Trends Immunol. 2016) and used this understanding of molecular processes to reprogram mature T cells into new stable phenotypes with additional functions (Hegazy et al., Immunity 2010). More recently, we showed a quantitative cytokine memory in individual cells. This means that a cell memorizes and stably maintains its individual production amount of a given cytokine (Helmstetter et al., Immunity 2015). We suggest that chondrocytes feature similar subtypes, differentiation programs, and possibilities of reprogramming. Ultimately, we want to reprogram the chondrocyte phenotypes that lead to the development of OA in patients in such a way as to achieve a long-lasting cartilage build-up.
Keywords
Osteoarthritis pathogenesis
Chondrocyte differentiation
Bone cell development
Bone angiogenesis
Lymphocyte differentiation
Immunological memory
Group leader
Univ.Prof. Dr. rer. nat. Max Löhning
Scientists
Dr. rer. nat. Caroline Helmstetter
Dr. phil. Roman Marek
Dr. biol. hum. Anna Rapp
Ph.D. Philippe Saikali
Daniel Schulz
Dr. rer. nat. Ping Shen
PhD students
Tobias Brunner
Nayar Duran
Maria Dzamukova
Adrian Madrigal-Avilés
Dominik Niesen
Mai Dan Nguyen
Valerie Plajer
Sebastian Serve
Domonkos Vince Varga
Technicians
Vivien Holecska
Isabel Panse
Carola Rüster
Peihua Wu
Secretariat
Christiane Golz-Wehner
- Helmstetter C, Flossdorf M, Peine M, Kupz A, Zhu J, Hegazy AN, Duque-Correa MA, Zhang Q, Vainshtein Y, Radbruch A, Kaufmann SH, Paul WE, Höfer T, Löhning M. Individual T helper cells have a quantitative cytokine memory. Immunity. 2015; 42:108-22.
- Baumann C, Bonilla WV, Fröhlich A, Helmstetter C, Peine M, Hegazy AN, Pinschewer DD, Löhning M. T-bet- and STAT4-dependent IL-33 receptor expression directly promotes antiviral Th1 cell responses. Proc Natl Acad Sci USA. 2015; 112:4056-61.
- Bhattacharya* A, Hegazy* AN, Deigendesch N, Kosack L, Cupovic J, Kandasamy RK, Hildebrandt A, Merkler D, Kühl AA, Vilagos B, Schliehe C, Panse I, Khamina K, Baazim H, Arnold I, Flatz L, Xu HC, Lang PA, Aderem A, Takaoka A, Superti-Furga G, Colinge J, Ludewig B, Löhning# M, Bergthaler# A. Superoxide dismutase 1 protects hepatocytes from type I interferon-driven oxidative damage. Immunity. 2015; 43:974-86. */# equal contributions.
- Peine M, Marek RM, Löhning M. IL-33 in T cell differentiation, function, and immune homeostasis. Trends Immunol. 2016; 37:321-33.
- Siede J, Fröhlich A, Datsi A, Hegazy AN, Varga DV, Holecska V, Saito H, Nakae S, Löhning M. IL-33 receptor-expressing regulatory T cells are highly activated, Th2 biased and suppress CD4 T cell proliferation through IL-10 and TGFβ PLoS One. 2016; 11:e0161507.
University of Colorado, Denver, CO, USA:
Prof. Dr. Charles A. Dinarello
Kennedy Institute of Rheumatology, University of Oxford, UK:
Prof. Dr. Fiona Powrie
Prof. Dr. Tonia Vincent
Dr. Anjali Kusumbe
NIH, NIAID, Bethesda, MD, USA:
Dr. Jinfang Zhu
Dr. Dragana Janković
University of Tokyo, Japan:
Prof. Dr. Susumu Nakae
Chiba University, Japan:
Prof. Dr. Toshinori Nakayama
ETH & Universitätsspital Zürich, Schweiz:
Prof. Dr. Rolf M. Zinkernagel
Prof. Dr. Hans Hengartner
Universität Basel, Schweiz:
Dr. Weldy Bonilla
Prof. Dr. Daniel D. Pinschewer
Prof. Dr. Mike Recher
Universität Genf, Schweiz:
Prof. Dr. Doron Merkler
Kantonsspital St. Gallen, Schweiz:
Prof. Dr. Lukas Flatz
Universität Lausanne, Schweiz:
Prof. Dr. Sanjiv Luther
Research Center for Molecular Medicine of the Austrian Academy of Science, Wien, Österreich:
Dr. Andreas Bergthaler
Dr. Rolf M. Schwiete Forschungsbereich für Arthrose, Orthopädische Universitätsklinik Friedrichheim, Frankfurt am Main:
Prof. Dr. Andrea Meurer
Prof. Dr. Frank Zaucke
Universitätsklinikum Essen:
Prof. Dr. Karl S. Lang
Universität Düsseldorf:
Prof. Dr. Philipp A. Lang
Deutsches Krebsforschungszentrum (DKFZ), Heidelberg:
Prof. Dr. Thomas Höfer
Dr. Christoph Kommer
Dr. Qin Zhang
FU Berlin, Veterinärmedizin:
Prof. Dr. Susanne Hartmann
Dr. Sebastian Rausch
MPI für Infektionsbiologie, Berlin:
Prof. Dr. Stefan Kaufmann
Prof. Dr. Arturo Zychlinsky
Dr. Nikolaus Deigendesch
Dr. Andreas Kupz
Charité, Berlin:
Prof. Dr. Gerd-Rüdiger Burmester
Dr. Dr. Ahmed N. Hegazy
Prof. Dr. Frank Buttgereit
Prof. Dr. Georg Duda
Dr. Michael Fuchs
Marie-Jacque Reisener, Assistenzärztin in Weiterbildung
Lisa Renner, Assistenzärztin in Weiterbildung
Dr. Clemens Gwinner
Dr. Tobias Jung
PD Dr. Matthias Pumberger
Dr. Melba Muñoz
Dr. Anja A. Kühl
Prof. Dr. Marcus Maurer
Prof. Dr. Martin Metz
Prof. Dr. Carsten Perka
Dr. Philipp von Roth
Prof. Dr. Hans-Dieter Volk
Prof. Dr. Margitta Worm
Miltenyi Biotec, Bergisch Gladbach:
Dr. Mario Assenmacher
Dr. Andreas Bosio
Dr. Anne Richter
- Willy Robert Pitzer Stiftung: Pitzer-Labor Arthroseforschung
- Schweizerischer Nationalfonds (SNF): Sinergia CRSII3_160772 I 1
