Evaluation of a Small-Molecule Inhibitor of DDR2 as a Drug in Treatment of Osteoarthritis
Technical Report,15 Apr 2018,14 Apr 2019
Harvard University, Boston President and Fellows of Harvard College Boston United States
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Osteoarthritis OA, including post-traumatic osteoarthritis PTOA, is the most common form of the arthritis affecting more than 27 million Americans. It is estimated that 12 percent of the current OA population suffers from post-traumatic injuries. Despite myriad research in the field, there are presently no known disease-modifying OA drugs DMOADs to treat the disease. Over the past few years, the data from several independent research groups indicate a novel and key, irreversible, step leading to joint destruction. This pivotal step occurs once the chondrocytes have degraded their pericellular matrix, exposing the surface of the chondrocytes to collagen type II. Collagen type II then binds to the chondrocyte cell surface via a tyrosine kinase receptor known as discoidin domain receptor 2 DDR2. This induces the synthesis and release of matrix metalloproteinase 13 MMP-13, an enzyme with the unique ability to degrade collagen type II and aggrecan. The end result is OA. Thus, targeting the induction of MMP-13, from the inhibition of DDR2 activity, is one of the key steps in preventing the irreversible joint destruction. In this investigation, we will determine whether or not a novel small-molecule inhibitor of DDR2 can inhibit the induction of MMP-13 in chondrocytes, thus retarding the progression of OA.
- Medicine and Medical Research