Biomechanics of the Pericellular Matrix (PCM): Roles in Cartilage Development and Osteoarthritis
Monday, October 30, 2017
3:00 PM-5:00 PM
BIOMED PhD Research Proposal
Biomechanics of the Pericellular Matrix: Roles in Cartilage Development and Osteoarthritis
Daphney Chery, PhD Candidate, School of Biomedical Engineering, Science and Health Systems
Lin Han, Assistant Professor, School of Biomedical Engineering, Science and Health Systems
The pericellular matrix (PCM) is a narrow 3-5 μm thick tissue surrounding the chondrocytes in articular cartilage. The PCM of normal cartilage is defined by the exclusive presence of type VI collagen. Moreover, in comparison to the further-removed territorial/interterritorial matrix (T/IT-ECM), it also has a higher concentration of proteoglycans, perlecan, types II and IX collagen and fibronectin. The PCM lies in the intermediate space between the T/IT- ECM and the cell and has distinctive mechanical and structural properties from the T/IT-ECM. Being the immediate microenvironment of each cell, it has been hypothesized that the PCM serves as a transducer for biomechanical, biophysical and biochemical signals between the cell and the ECM. For example, studies have found that the PCM is critical to many mechanosensitive cell activities such as adhesion, migration, solute transport and mechanotransduction. This renders it important to understand the biomechanical and structural properties of cartilage PCM.
This study will generate new knowledge on the biomechanics and structure of the PCM in articular cartilage during the development and the progression of OA. First, we will study the effects of decorin on the structure and mechanical properties of murine articular cartilage at the fetal, juvenile and mature stages. This will provide a molecular benchmark for understanding the governing effects of decorin on articular cartilage during maturation. Second, since murine model provides a unique tool to study OA pathogenesis in vivo, we will for the first time, quantify the structure and mechanical properties of the PCM during the initiation and progression of OA in wild-type articular cartilage using our destabilization of medial meniscus mice model. This will provide a basis for understanding whether PCM can serve as a potential target for early OA detection.