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Roles of Decorin in Cartilage Biomechanical Function and Osteoarthritis

Wednesday, January 17, 2018

4:00 PM-5:30 PM

BIOMED Seminar

Roles of Decorin in Cartilage Biomechanical Function and Osteoarthritis

Lin Han, PhD
Assistant Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Mechanical properties of connective tissues are determined by the composition and structure of the extracellular matrix (ECM). Assembly of the ECM is governed by synergistic activities of regulatory matrix molecules, such as small leucine rich proteoglycans (SLRPs). In fibrous tissues including tendon and skin, SLRPs can bind to collagen fibril surface to regulate fibril diameter and spacing, thereby the ECM mechanical properties.

Our study discovered a new critical role of the most abundant SLRP, decorin, in articular cartilage biomechanics. The ECM of cartilage is composed of not only type II/IX/XI collagen fibrils, but also the large proteoglycan, aggrecan. In decorin-null (Dcn-/-) murine cartilage, while the structural changes of collagen are mild, there is a significant reduction of aggrecan content. In accordance, Dcn-/- cartilage shows substantially impaired mechanical properties, including reduced elastic modulus and much elevated hydraulic permeability. After the destabilization of the medial meniscus (DMM) surgery, Dcn-/- mice develop more severe osteoarthritis (OA) than the wild-type control, signified by the reduced modulus, accelerated aggrecan depletion and pronounced surface fibrillation.

These results underscore the importance of decorin in proper mechanical functioning of cartilage. Since decorin can bind to both collagen and aggrecan, we hypothesize that decorin functions as a “linker” to connect aggrecan with adjacent aggrecan molecules and with collagen fibrils, and thus, plays an indispensable role in the overall structural integrity of cartilage ECM in both healthy and OA tissues.

Lin Han obtained his BE degree at Tsinghua University in P. R. China, and his PhD degree at the Massachusetts Institute of Technology. His PhD thesis focused on the molecular, cellular, and tissue nanomechanics of cartilage. Dr. Han later worked as a post-doctoral associate in the Department of Materials Science and Engineering and the Center for Biomedical Engineering at MIT, where he continued the exploration of nanostructure and nanomechanics of soft and hard biological tissues. During this period, he developed an array of unique nanomechanical tools to uncover the molecular origins of cartilage development, function and disease.

In November 2012, Dr. Han joined the School of Biomedical Engineering, Science and Health Systems at Drexel University as an assistant professor. His current research seeks inspiration from the nanoscale structure-mechanics of synovial tissues to their development and maturation, aging and osteoarthritis (OA) progression, with a special focus on hyaline articular cartilage and fibrocartilage (meniscus and temporomandibular joint). The ultimate goal is to provide a fundamental knowledge basis for the application of disease diagnostics, tissue regeneration, and bio-inspired material design.

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