The relationship between articular cartilage damage and lubricin integrity following injury and in inflammatory arthritis
The two major constituents of cartilage are collagen type II (CII) and aggrecan. Osteoarthritis (OA) and rheumatoid arthritis (RA) are characterized by irreversible damage to cartilage. Knee injury is recognized as a cause of secondary OA. Understanding the mechanism by which OA develops following injury can lead to emergence of intervention strategies to slow the progression of OA. ^ Lubricin is a protein that is responsible for the lubrication of articular surfaces. The loss of lubricin can precipitate cartilage damage. This research aimed to investigate the role that proteolytic degradation of lubricin, following knee injury, plays in cartilage damage. The hypothesis of the investigation was that lubricin is susceptible to proteolytic degradation by proteases, whose expression is up-regulated following inflammatory insults. The proteolytic degradation of lubricin increases coefficient of friction (μ) of SF and of whole articular joints leading to wear-induced damage. ^ In manuscript I, cartilage damage was established in the SF aspirated from patients with knee joint synovitis (KJS) using CII-specific ELISA assays. The CII peptides in the SF aspirated from patients with KJS were found to be significantly higher than CII peptides in the SF from patients with OA indicating an active matrix-degrading process following knee injury. ^ In manuscript II, the lubricating properties of SF from patients with KJS and RA were assayed in a friction apparatus. These SF samples exhibited lowered lubricating ability compared to control SF. Time-dependent loss of SF's lubricating property was also demonstrated following injury in rabbits. ^ In manuscript III, the effects of cathepsin B and neutrophil elastase on lubricin were studied. Cathepsin B, played an important role in the degradation of lubricin following inflammation and in inflammatory arthritis. ^ In manuscript IV, a rat model was employed to study the effects of arthritis initiation and progression on the integrity and function of lubricin. The progression of inflammation was correlated with μ of arthritic joints and articular cartilage damage. Synovial tissue inflammation was observed following arthritis induction. Inflammation contributed to decreased lubricin secretion and elevated cathepsin B synthesis by synovial tissues. Combined, these effects caused the observed elevation in μ of arthritic joints. ^
Health Sciences, Pharmacology|Health Sciences, Pathology
Khaled Ahmed Elsaid,
"The relationship between articular cartilage damage and lubricin integrity following injury and in inflammatory arthritis"
Dissertations and Master's Theses (Campus Access).