Post-traumatic osteoarthritis 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. This is because the pathogenesis of PTOA is still not well understood, despite advances in research. Although PTOA is considered a whole joint disease, the irreversible breakdown of articular cartilage is considered the key hallmark of PTOA.

Articular cartilage is a smooth, white highly-specialized tissue that lines diathrodial joints. It is comprised of a dense extracellular matrix (ECM) with a sparse distribution of cells called chondrocytes. During PTOA, there is a disturbance in the homeostasis of the anabolic-catabolic activities of chondrocytes leading to disruption of cell-ECM interplay. This renders it important to understand the immediate microenvironment of the chondrocytes, 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 the chondrocyte perceives is likely to be influenced, and potentially regulated, by the properties of the PCM. Furthermore, enzymes and growth factors released by the chondrocytes must first be passed through the PCM, where they may be preserved or altered. In PTOA, the PCM undergoes structural changes as well as significant loss of its’ biomechanical properties. Additionally, the PCM has been shown to soften and expand during the development of PTOA. Thus, studying the PCM during PTOA and development could provide a basis for therapeutic interventions and better understanding of cellular stress and strain.

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 wildtype 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 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.