Pitzer Laboratory of Osteoarthritis Research

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 and used this understanding of molecular processes to reprogram mature T cells into new stable phenotypes with additional functions. 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. 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.

Group leader
Univ.Prof. Dr. rer. nat. Max Löhning

Scientists
Dr. Ping Shen
Dr. Philippe Saikali
Dr. Tobias Brunner

PhD students
Nayar Alejandro Durán Hernández
Jelizaveta Fadejeva
Yujie Dai
Xiaohui Liu
Xu Liang
Shilei Wu

Technicians
Peihua Wu
Vivien Holecska

Eicke Latz, Gerhard Krönke, Mir-Farzin Mashreghi, Ahmed Hegazy, Chiara Romagnani, Andreas Diefenbach, Carsten Perka, Tobias Winkler, Matthias Pumberger

Tilman Grune, DIfE, Potsdam

Frank Zaucke, Frankfurt/Main; Bent Brachvogel, Köln; Ralf Kühn, MDC, Berlin; Thomas Höfer, Heidelberg; Karl Lang, Essen; Philipp Lang, Düsseldorf

Tonia Vincent, Oxford, UK; Daniel Pinschewer, Basel, Switzerland; Charles Dinarello, Denver, CO, USA; Jeff Zhu, NIH-NIAID, Bethesda, MD, USA