Roles of Decorin in the Assembly and Retention of Nascent Cartilage ECM Constituents
Wednesday, June 4, 2025
2:00 PM-4:00 PM
BIOMED PhD Research Proposal
Title:
Roles of Decorin in the Assembly and Retention of Nascent Cartilage ECM Constituents in Native and Regenerative Matrices
Speaker:
Thomas Li, 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:
Articular cartilage is a specialized load-bearing tissue whose mechanical resilience depends on the structural integration of its two primary extracellular matrix (ECM) constituents: collagen II fibrils and the aggrecan supramolecular network. Disruption of this integration, particularly through aggrecan loss, is a hallmark of early osteoarthritis (OA) and is not adequately addressed by current regenerative strategies. Emerging evidence highlights the role of decorin, a small leucine-rich proteoglycan, in coordinating ECM architecture, yet its precise function in regulating nascent matrix assembly and retention remains poorly understood. This thesis elucidates how decorin modulates the formation and stability of newly synthesized cartilage ECM components under both normal and degenerative conditions.
Using bio-orthogonal click-labeling, we visualized the temporal and spatial deposition of nascent glycosaminoglycans and proteins in both explant and 3D methacrylated hyaluronan (MeHA) hydrogel models. We found that decorin loss accelerates the release of nascent aggrecan without affecting collagen II synthesis, suggesting a role in proteoglycan retention. Exogenous decorin treatments mitigated matrix loss only when administered before catabolic stimulation, indicating protective effects are contingent on early matrix incorporation. Surface plasmon resonance further revealed high-affinity binding between decorin and aggrecan and enhanced ternary interactions between decorin, collagen II, and aggrecan, supporting its role as a “physical linker."
In MeHA hydrogels, decorin overexpression via AAV2 gene therapy is hypothesized to improve matrix retention, collagen network formation, and mechanotransduction under dynamic loading. Together, these findings establish decorin as a key mediator of cartilage ECM integration and resilience, with translational implications for regenerative medicine. By advancing our understanding of how nascent matrix structure is regulated, this work sets the stage for decorin-based therapeutic strategies aimed at enhancing tissue repair and delaying OA progression.
Contact Information
Natalia Broz
[email protected]