Accession Number : AD1003212


Title :   Identification and Manipulation of a Novel Signaling Mechanism to Improve Articular Cartilage Restoration After Posttraumatic Joint Injury


Descriptive Note : Technical Report,30 Sep 2013,29 Sep 2014


Corporate Author : University of California, Los Angeles Los Angeles United States


Personal Author(s) : Evseenko,Denis


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1003212.pdf


Report Date : 01 Oct 2014


Pagination or Media Count : 8


Abstract : Injured articular cartilage evidences little intrinsic regenerative capacity. When healing does occur, either as a result of a full thickness defect or microfracture surgery designed to mimic this event, mesenchymal cells from the bone marrow (BM-MSCs) produce disorganized collagen, with a pronounced bias toward collagen I (COL I) in lieu of collagen II (COL II). As a result, the newly-formed fibrocartilage has poor biomechanical properties and often evidences poor integration with the surrounding, native COL II-expressing cartilage, thus priming the tissue for subsequent degeneration. Identification of factors that drive fibrocartilage generation at the site of injury defines a new potential avenue of intervention in the field of cartilage restoration. We defined the lysophosphatidic acid (LPA)-autotaxin (ATX; encoded by the ENPP2 gene) signaling axis as an important mediator of fibrocartilage formation both in vitro and in vivo. Addition of LPA to cultures of human chondrocytes and BM-MSCs substantially increased expression of COL I at the expense of COL II; this outcome could be reversed by small molecule or genetic inhibition of ATX activity. Importantly, drug-based inhibition of ATX activity led to reduced COL I expression and increased the secretion of COL II in a rat model similar to microfracture, thereby improving the quality of neocartilage formed after full-thickness injury.


Descriptors :   FIBROSIS


Distribution Statement : APPROVED FOR PUBLIC RELEASE