QUANTIFICATION OF MINERALIZATION AROUND THE MURINE KNEE IN RESPONSE TO UBIQUITOUS INTEGRIN α1B1 AND CARTILAGE-SPECIFIC TBRII KNOCK-OUT

Abstract

Osteoarthritis is the most common form of arthritis. Genetic models have been developed to determine if and how a targeted gene may influence cartilage degenerative changes. The itga1-null mouse model has an inhibited integrin α1B1 through a ubiquitous integrin α1 subunit knockout, which leads to fibrosis in articular cartilage through excessive signalling from transforming growth factor beta (TGFB). Depleting this TGFB signalling is proposed to have a protective effect on cartilage. This project is part of a foregoing study where a cartilage-specific knockout of TGFB receptor type II (TBRII) was used to deplete TGFB signalling in articular cartilage of the itga1-null mice to reduce the severity of cartilage degradation. This project continues the analysis of the genetic model into bone architecture at the knee. Mouse hindlimbs were scanned at a 13μm resolution using micro-computed tomography and segmented into 3D datasets containing calcified tissues and bone of the knee and surroundings. Quantification methods for trabecular bone parameters (bone volume fraction, trabecular separation, and trabecular thickness) and ectopic calcification of soft tissues were developed. Loss of trabecular bone around the involved joint is a hallmark of post-traumatic osteoarthritis. However, the results from this study showed no significant changes in trabecular bone of itga1-null mouse knees despite observing severe osteoarthritic changes in the adjacent cartilage. There were no significant effects in peri-articular trabecular bone when the TBRII knockout in cartilage was activated, but there were significant increases in ectopic calcifications of the menisci and collateral ligaments. These ectopic calcifications were also seen in tamoxifen control mice, suggesting that tamoxifen, along with TBRII depletion in cartilage, had a role in increased abnormal calcifications. Although integrin α1B1 inhibition appears to have an important role in cartilage degeneration, it does not appear to influence the bony changes that normally accompany post-traumatic arthritis.