Deutsch
Löhning lab
Biological regeneration of cartilage by selection and reprogramming of chondrocytes
Pitzer Lab Osteoarthritis Research
The Pitzer Laboratory of Osteoarthritis Research investigates the cellular and molecular mechanisms leading to the development of osteoarthritis (OA). Our goal is biological regeneration of cartilage in affected joints.
OA is the most frequently occurring joint disease among adults worldwide and the most important cause of disability among elderly people in Germany. This chronic degenerative disease 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. This applies particularly to differentiation and apoptosis programs of these cells. So far, the chondrocytes’ in situ biology is understood only to some degree. Here, the biggest obstacles for further advancement in the research of these rare cells are (1.) their difficult accessibility and (2.) the limited possibilities to isolate and culture them without changing their phenotypes.
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. It is known that central transcription factors like SOX9 and RUNX2 regulate the chondrocytes’ development right up to hypertrophic and/or degenerative stages. Comparable processes take place in the immune system that can be regarded as a prototypical model of cell differentiation in a complex network responding to its environment. Here, our group’s accumulated knowledge on the (re-) programming of T cells will be transferred to chondrocytes and the field of OA research.
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). In addition, we 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 longlasting 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. Claudia Baumann
Dr. rer. nat. Caroline Helmstetter
Dr. phil. Roman Marek
Dr. rer. nat. Melba Muñoz
Dr. rer. nat. Michael Peine
Dr. biol. hum. Anna Rapp
Ph.D. Philippe Saikali
Dr. rer. nat. Daniel Schulz
Dr. rer. nat Ping Shen
Dr. rer. nat. David Zimmel
PhD students
Tobias Brunner, Nayar Duran, Maria Dzamukova
Adrian Madrigal-Avilés, Dominik Niesen, Mai Dan Nguyen
Valerie Plajer, Domonkos Vince Varga
Technicians
Sabine Ebel, 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 Jan 20; 42(1):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 Mar 31; 112(13):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 Nov 17; 43(5):974-86. */# equal contributions.
Peine M, Marek RM, Löhning M. IL-33 in T cell differentiation, function, and immune homeostasis. Trends Immunol. 2016 May; 37(5):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 release. PLoS One. 2016 Aug 22; 11(8):e0161507.
University of Colorado, Denver, CO, USA:
Prof. Dr. Charles A. Dinarello
NIH, NIAID, Bethesda, MD, USA:
Dr. Jinfang Zhu
Dr. Dragana Jankovic
University of Tokyo, Japan:
Prof. Dr. Susumu Nakae
Chiba University, Japan:
Prof. Dr. Toshinori Nakayama
University of Oxford, UK:
Prof. Dr. Fiona Powrie
Dr. Dr. Ahmed N. Hegazy
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
Universitätsklinikum Essen:
Prof. Dr. Karl S. Lang
Universität Düsseldorf:
Prof. Dr. Philipp A. Lang
Deutsches Krebsforschungszentrum (DKFZ), Heidelberg:
Prof. Dr. Thomas Höfer
Dr. Michael Floßdorf
Dr. Yevgeniy Vainshtein
Dr. Qin Zhang
Universität Marburg:
Prof. Dr. Michael Lohoff
Universität Giessen:
Prof. Dr. Christoph G. Grevelding
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
Prof. Dr. Frank Buttgereit
Prof. Dr. Georg Duda
Dr. Michael Fuchs
Dr. Anja A. Kühl
Prof. Dr. Marcus Maurer
Prof. Dr. Martin Metz
Prof. Dr. Carsten Perka
Dr. Philipp von Roth
Prof. Dr. Alexander Scheffold
PD Dr. Uta Syrbe
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
- EU: FP7, Marie Curie ITN QuanTI
- MPG: IMPRS-IDI
