| Start Date: | 1/28/2019 | Start Time: | 3:00 PM |
| End Date: | 1/28/2019 | End Time: | 5:00 PM |
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Event Description
BIOMED PhD Thesis Defense
Title:
Biomechanics of the Pericellular Matrix: Roles in Cartilage Development and Osteoarthritis
Speaker:
Daphney Chery, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Advisor:
Lin Han, PhD
Associate Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University
Abstract:
Post-traumatic osteoarthritis (PTOA) is caused by joint injuries leading to progressive degeneration of articular cartilage. PTOA is prevalent in young adults and acute symptoms include swelling, severe pain and synovial effusion. Currently, PTOA is not clinically diagnosed until the onset of the symptomatic phase and there are no effective pharmacological treatments that slows or halts disease progression. To this end, both cartilage cells (chondrocytes) and extracellular matrix (ECM) have been extensively studied, in health and in diseased tissues. Yet, there is limited understanding of their intermediary microstructural unit, the pericellular matrix (PCM).
The PCM is a narrow 3-5 μm thick tissue surrounding the chondrocytes in articular cartilage. The PCM of normal cartilage surrounds the chondrocytes, separating the cell from the ECM and has distinctive mechanical and structural properties from the ECM. Because the PCM surrounds each cell, any biochemical or biophysical signal which the chondrocyte perceives is likely to be influenced, and potentially regulated, by the properties of the PCM. In OA, the PCM is expected to be a key player. The two cartilage PCM-specific molecules, collagen VI and perlecan, are essential for its function. Loss of collagen VI (in Col6a1-/- mice) leads to reduced PCM modulus, increased chondrocyte osmotic responses, and altered susceptibility to OA. Reduction of perlecan (in Hspg+/- mice) leads to reduced cartilage tissue modulus, while absence of perlecan (Hspg-/-) results in lethal skeletal dysplasias. In addition, the importance of PCM is highlighted by the weakening of PCM in human OA cartilage. Thus, studying the PCM of articular cartilage can yield new targets for early OA detection and intervention and can also help develop new methods to preserve the native PCM to aid in cartilage regeneration.
This study will generate new knowledge on the biomechanics and structure of the PCM and chondrocyte mechanotransduction in articular cartilage during the progression of PTOA and articular cartilage development. First, 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 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. Second, we will study the effects of decorin, the most abundant small leucine rich proteoglycan, on the structure and mechanical properties of murine articular cartilage at the fetal, juvenile and adult ages. This will provide a molecular benchmark for understanding the governing effects of decorin on articular cartilage PCM during post-natal development. |
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Location:
Bossone Research Center, Room 709, located at 32nd and Market Streets. |
Audience:
Undergraduate StudentsGraduate StudentsFacultyStaff |
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