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Roles of Collagen V in the Joint Development and Osteoarthritis of Temporomandibular Joint

Thursday, June 28, 2018

12:00 AM-12:00 AM

BIOMED PhD Research Proposal

Roles of Collagen V in the Joint Development and Osteoarthritis of Temporomandibular Joint

Prashant Chandrasekaran, PhD Candidate, School of Biomedical Engineering, Science and Health Systems, Drexel University

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

The articular disc and mandibular condyle cartilage in the temporomandibular joint (TMJ) endows the joint with its specialized biomechanical functions enabling everyday speaking and chewing. In this unique diarthrodial joint, the disc is collagen I-dominated fibrocartilage, while the condyle consists of a bi-layered layout of fibrocartilage layer covering the collagen II-dominated hyaline region. TMJ osteoarthritis is a debilitating disease affecting 10-16% of the population, and is characterized by the irreversible degradation of these cartilaginous tissues leading to joint pain and disc displacement.

The lack of strategies available to effectively treat TMJ OA or repair damaged TMJ tissues is due to the limited understanding of the structure-function principles of the specialized TMJ cartilage extracellular matrix (ECM). This motivated us to study the role of collagen V in regulating normal TMJ cartilage ECM assembly and TMJ degradation in OA. Collagen V is the key regulator of collagen I fibril assembly, serving as the nucleation core for initiating collagen I fibrillogenesis. Its importance to human TMJ function is illustrated by the higher incidences of TMJ OA in patients with classical Ehlers-Danlos Syndrome (EDS), a genetic disorder due to the deficiency of collagen V. Indeed, our preliminary data showed that in collagen V-deficient mice (Col5a1+/-), the TMJ cartilage exhibits thickened collagen fibrils and impaired biomechanical properties. Furthermore, these defects are present in not only collagen I-dominated fibrocartilage, but also, unexpectedly, in collagen II-based hyaline cartilage. This indicates that collagen V could play a potentially important role in regulating the assembly of hyaline cartilage in TMJ, via a mechanism which is currently unknown. Thus, the overall objective of this study is to determine the role of collagen V in the structure and biomechanical functions of TMJ cartilage during normal joint development and in TMJ OA.

Our central hypothesis is that collagen V plays critical roles in regulating the fibril structure and mechanical properties of both fibro- and hyaline cartilage in TMJ during normal joint growth and in TMJ OA. We will test this hypothesis in two central aims. First, we will determine the roles of collagen V in TMJ cartilage structure and function during normal joint growth. Second, we will test if deficiency of collagen V increases the susceptibility to TMJ OA and delineate the roles of collagen V in degradation of TMJ cartilage. We will utilize novel atomic force microscopy (AFM) based nanoindentation technique to quantify the biomechanical properties of these murine tissues. Finally, studying the impacts of collagen V on the structure and mechanical properties of TMJ will provide direct insights into the higher incidents of TMJ OA in EDS patients. This knowledge will provide a basis for designing new strategies to improve TMJ cartilage regeneration and to treat TMJ OA by modulating the assembly and degradation of the hybrid fibro-hyaline ECM via collagen V.

Contact Information

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