Regulatory Roles of Decorin in Maintenance & Remodeling of Articular Cartilage Matrix During Aging
Monday, April 15, 2024
1:00 PM-3:00 PM
BIOMED PhD Research Proposal
Title:
The Regulatory Roles of Decorin in the Maintenance and Remodeling of Articular Cartilage Matrix During Aging
Speaker:
Mingyue Fan, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Advisor:
Lin Han, PhD
Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University
Details:
Osteoarthritis (OA) is the most common form of degenerative joint disease in the world, affecting more than 27 million people in the US and costing nearly over two hundred billion dollars annually. Aging is the leading factor of spontaneous OA that affects half of the population over the age of 65. In OA, articular cartilage undergoes irreversible breakdown, leading to severe joint pain and limited joint motion for the patients. Until today, there are limited success in treating OA or restoring cartilage function. Cartilage aging is associated with concomitant changes in both chondrocyte activities and extracellular matrix (ECM) properties. In contrast to the tremendous efforts dedicated to understanding aging cells, there is a paucity of knowledge of how aging affects the integrity and biomechanical functions of cartilage ECM at the molecular level. The ECM is a hydrated composite of a collagen II/IX/XI network that entraps aggrecan. They resist tensile stress and provide load bearing and energy dissipating functions. Besides the major two components, other regulatory matrix molecules, including minor collagens and proteoglycans work in concert that regulate the integrity, function and pathology of the cartilage. The activities of these molecules are not well understood in the context of aging.
Our previous studies found that decorin, a small leucine-rich proteoglycan, plays an indispensable role in regulating the integrity of the aggrecan network in cartilage ECM during post-natal growth and attenuates surface fibrillation in post-traumatic OA. Building on these findings, in this work, we queried the role of decorin in regulating cartilage ECM maintenance and cell-ECM interactions during aging. To do so, we first determined changes in cartilage mechanical and mechanobiological properties during aging, which laid down the benchmarks for investigating cartilage degeneration during aging. Second, we established cartilage-specific decorin inducible knockout mice to delineate the role of decorin in cartilage during aging.
In this model, we found loss of decorin resulted in accelerated surface fibrillation and depletion of proteoglycans, which leads to substantial weakening of cartilage tissue and loss of chondrocyte in situ calcium signaling. Furthermore, on femoral condyle surface, we found the complete erosion of articular cartilage, followed by the infiltration of a population of highly metabolically active cells that express a high level of fibrotic genes, evidence pronounced joint damage and aberrant remodeling. These findings highlighted the novel and important roles of decorin in maintaining cartilage ECM integrity and inhibiting cartilage surface fibrillation during aging. Results from this study deepen our knowledge on the biomechanical and mechanobiological changes of cartilage ECM during aging, which facilitates the development of new strategies to alleviate aging-induced OA. Also, the understanding of decorin’s role in maintaining cartilage surface integrity will enable the use of decorin as a target for ameliorating OA and provide insights for using decorin to reduce fibrocartilage formation when designing new biomaterials for cartilage regeneration.
Contact Information
Natalia Broz
njb33@drexel.edu