University Hospital for Orthopaedics

Joint articular cartilage, due to the lack of a perichondrium, is considered to have limited regenerative capacity and, as a result, can be worn down by injuries or misalignment leading to osteoarthritis. In a realistic osteochondral model, artificial regeneration matrices are being studied for their ability to support new cell ingrowth and functionality. The aim is to find long-term alternatives to artificial joint replacement.

In cell differentiation, as observed in tumors, multiple signaling pathways are involved. We analyze how the overexpression of specific genes, which influences cellular protein synthesis, correlates with observed changes in cellular biomechanical properties and the effects of radiation therapies. This comparison allows us to draw conclusions about the metastatic potential (cell migration) of these cells.

Joint cartilage endures significant compressive and shear forces during loading. Within this cartilage, chondrocytes are scattered throughout an extensive extracellular matrix, which is engineered to handle these high demands with minimal friction. Surrounding each chondrocyte is a specialized form of extracellular matrix known as the pericellular matrix. This cocoon-like layer not only offers mechanical protection but also appears to facilitate coordinated signaling from the extracellular matrix into the cell. We delve into the intricate composition and functional roles of this pericellular matrix to better understand its impact on cartilage health and functionality.

Imaging techniques typically capture qualitative morphological changes in tissues, which are then correlated with quantitative data from biochemical analyses. In our lab, we take this a step further by measuring mechanical changes in tissues and cells at the microscopic scale. This approach enables us to directly translate structural observations into functional insights.

The pericellular matrix (PCM) is crucial for mechanotransduction in chondrocytes. To explore how a compromised PCM affects chondrocyte biochemical signaling, we examine calcium signaling dynamics. By enzymatically isolating chondrocytes and partially degrading their PCM with matrix metalloproteinases, we can probe the impact on cellular responses. Mechanical stimulation is applied using atomic force microscopy (AFM), and calcium influx is assessed through fluorescence microscopy. Our aim is to elucidate the PCM's specific role in mediating cellular mechanotransduction.

As a load-bearing tissue, articular cartilage houses a range of mechanosensitive calcium channels that react to mechanical forces and loading. We are investigating the roles of ion channels like Piezo-1, Piezo-2, and TRPV-4 in calcium signaling within chondrocytes. By comparing the expression of these channels in healthy versus osteoarthritic cartilage, our goal is to identify the key signaling pathways that drive the onset and progression of osteoarthritis.

We investigate the dual role of glucocorticoids (Cortisone) in knee joint tissue regeneration and degeneration.