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Investigating the Chondroprotective Nature of Extracellular Matrix Protein Matrilin-3

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Abstract:
Matrilin-3 (MATN3) is a member of the matrilin family of extracellular matrix (ECM) proteins. It is specifically found in cartilage where it is classically believed to function as a structural protein that physically stabilizes tissue integrity. Mutations in the MATN3 gene are associated with a variety of skeletal diseases with varying severity including chondrodysplasia and hand osteoarthritis (HOA). Furthermore, a recent study has shown that mice deficient in the functional MATN3 gene appear to undergo relatively normal skeletal development, yet they exhibit higher and earlier incidences of osteoarthritis (OA). Therefore, normal MATN3 prevents OA pathogenesis in vivo. Currently it is not known how MATN3 protects cartilage tissue from OA; however, the present study shows for the first time that MATN3 can regulate certain cartilage homeostasis markers. This study utilizes gene expression and protein analysis to investigate the underlying biology that confers chondroprotectivity of MATN3 by investigating its effects on both mature chondrocytes and mesenchymal stem cells (MSCs) of the chondrogenic lineage. It also employs PI3K and EGFR inhibitor studies to sheds light on key cell signaling pathways that are vital for the protective role(s) of MATN3 in chondrocytes.
Notes:
Thesis (Ph.D. -- Brown University (2013)

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Citation

Jayasuriya, Chathuraka T., "Investigating the Chondroprotective Nature of Extracellular Matrix Protein Matrilin-3" (2013). Pathobiology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z0GQ6W31

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