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Title: Understanding the role of ADAM15 in osteoarthritis
Author: Yang, Chun-Yao
ISNI:       0000 0004 7430 615X
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2018
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A disintegrin and metalloproteinase 15 (ADAM15) is a member of the ADAM family of metalloproteases, which plays important roles in a wide variety of biological functions. A previous study demonstrated that Adam15-null mice developed accelerated age-dependent OA, suggesting that ADAM15 has protective effects in the joint. Despite this potentially important role, little is known about how ADAM15 exerts its biological functions or is regulated in joints. In this project, I demonstrated that ADAM15 expression in the joint decreases with age. This correlates with a decrease in IL-13 expression with age. I showed that IL-13 up-regulates ADAM15 in vitro, suggesting that reduced IL-13 expression with age may underlie the observed reduction in ADAM15 expression with age. In parallel, I showed that ADAM15 is not a highly active sheddase, as multiple mass spectrometry proteomic analyses did not identify convincing ADAM15 substrates. However, proteomic analysis of surface proteins in ADAM15-knockdown HTB-94 cells showed that ADAM15 may regulate the surface abundance of SLC26A2, an important sulfate transporter in cartilage. In summary, the reduction of ADAM15 in aged cartilage and, potentially, the consequent reduced cell surface level of SLC26A2 may elevate risk for OA in aged joints.
Supervisor: Troeberg, Linda ; Nagase, Hideaki Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available