Force-mediated dissociation of proteoglycan aggregate in articular cartilage

Abstract

Proteoglycan aggregate is the primary component in articular cartilage responsible for resisting compressive loading. It consists of a core molecule of hyaluronan and a number of side chains of aggrecan bound to hyaluronan non-covalently. The loss of aggrecan from articular cartilage is considered to be a major factor in the development of osteoarthritis. Though enzymatic digestion of aggrecan is believed to be responsible for the release of aggrecan from osteoarthritic cartilage, other mechanisms, such as direct force-mediated detachment of aggrecan from hyaluronan may also be involved. In this study, the rupture force of the single bond between hyaluronan and aggrecan in articular cartilage was directly quantified using experimental measurement and Monte Carlo simulation. Low rupture force of this bond, as determined in this study suggested a possible direct force-mediated detachment of aggrecan from proteoglycan aggregate in osteoarthritic cartilage.