ICMRS Scientific Frontier Webinar Series
Decorin: A Central Regulator of Cartilage Extracellular Matrix Health and Disease
Presented by Lin Han, Ph.D.
Associate Professor, School of Biomedical Engineering, Science and Health Systems, Drexel University
When: October 24, 2020 (Saturday) 9:00 PM Eastern Time (US and Canada)
October 24, 2020 (Saturday) 8:00 PM Central Time (US and Canada)
October 25, 2020 (Sunday) 9:00 AM Perth (Australia - Western Australia)
October 25, 2020 (Sunday) 11:00 AM Sydney (Australia - New South Wales)
Where: Zoom Video Conference link will be emailed to ICMRS members.
Short Biography: Dr. Lin Han is an associate professor in the School of Biomedical Engineering, Science and Health Systems at Drexel University. He obtained Ph.D. degree at MIT in 2007. His Ph.D. thesis focused on the molecular, cellular and tissue nanomechanics of cartilage. He later worked as a post-doctoral associate at MIT, where he continued the exploration of nanostructure and nanomechanics of soft and hard biological tissues. In 2012, Dr. Han joined Drexel University as an assistant professor. His research aims to tackle the interdisciplinary challenges in the development, degeneration, and regeneration of connective tissue extracellular matrix by integrating novel methods in nanotechnology, matrix biology, biomechanics and biomaterials. His current focus is on the roles of three matrix biomacromolecules, aggrecan, decorin and type V collagen.
Abstract: The extracellular matrix (ECM) of cartilage mainly consists of type II/IX/XI heterotypic collagen fibril network entrapping the large proteoglycan, aggrecan. Integrity of the ECM is essential for proper joint biomechanics and chondrocyte mechanoregulation. Currently, the limited understanding of cartilage ECM represents a major roadblock to the development of effective regeneration and disease intervention strategies. We discovered a critical role of decorin, a small leucine-rich proteoglycan (SLRP), in regulating cartilage ECM biomechanics and mechanobiology. In cartilage, decorin functions as a “physical linker” to increase the adhesion of aggrecan molecules, thereby strengthening the ECM integrity. With the loss of decorin, decorin-null murine cartilage develops a substantial reduction of aggrecan content, with mild changes in collagen nanostructure. These defects contribute to significantly impaired cartilage biomechanics, including reduced elastic modulus and elevated hydraulic permeability. Furthermore, this decorin loss-induced aggrecan reduction leads to impaired cartilage pericellular matrix at the microscale, resulting in demoted intracellular chondrocyte Ca2+ responses in situ. When subjected to the destabilization of the medial meniscus (DMM) surgery, decorin-null mice develop more severe osteoarthritis (OA) than the control, signified by the reduced modulus, accelerated aggrecan depletion and pronounced surface fibrillation. These results underscore the indispensable role of decorin in the overall structural integrity and mechanobiology of cartilage ECM in both healthy and OA tissues. Modulation of decorin activities could provide a novel path to improve the quality of engineered cartilage and attenuate the degeneration of cartilage in disease.
This webinar will be moderated by Dr. Sherry Liu, Associate Professor, Department of Orthopaedic Surgery, University of Pennsylvania.
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For more information, please contact:
Jean Jiang, PhD
Chair, Education Committee, ICMRS
Professor and Zachry Distinguished University Chair
Department of Biochemistry and Structural Biology
University of Texas Health Science Center at San Antonio