Evaluation of a Small-Molecule Inhibitor of DDR2 as a Drug in Treatment of Osteoarthritis
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2019
- Accession Number
- AD1094837
Entities
People
- Yefu Li
Organizations
- Harvard University