The Influence of Macromolecule Accumulation on Cartilage Mechanics and Chondrocyte Health

University Of Rochester, Rochester NY

Investigators

Abstract

This project will study the mechanics of articular cartilage. Articular cartilage covers and protects the ends of long bones to enable smooth and pain-free joint motion. Cartilage is surrounded by synovial fluid, a thick and viscous liquid that provides lubrication and nutrients for the tissue. Since synovial fluid is formed from filtered blood plasma, it contains plasma proteins such as albumin. Interestingly, concentrations of albumin and other plasma proteins are markedly increased in joints affected by osteoarthritis, a devastating disease whose most prominent feature is progressive cartilage breakdown. These large molecules (macromolecules) can enter cartilage through pores within the tissue, but it is not known whether their presence alter cartilage’s ability to resist mechanical forces and protect joints from damage. To address this knowledge gap, this work will test how solute buildup modifies cartilage function. The results of this study could one day impact clinical care for osteoarthritis by shedding light on how the molecular composition of synovial fluid – which may be modifiable through clinical interventions – affects cartilage mechanical properties and health. In addition to its scientific and clinical impacts, this study will also impact the greater Rochester NY community, as it will be carried out in conjunction with an educational program that provides local high school students with research experience, mentoring, and opportunities to mentor others. This project seeks to define how the response of articular cartilage to mechanical load is influenced by the accumulation of large soluble molecules within its pores, a phenomenon that has not been described previously despite decades of cartilage mechanics research. Based on our preliminary work, the central hypothesis that will be tested in the current study is that accumulating a critical concentration of soluble molecules larger than a critical size is detrimental to cartilage health because the absorbed molecules increase tissue permeability, leading to an altered time-dependent mechanical response. Moreover, accumulation of large solutes increases over the lifespan, potentially contributing to joint disease pathogenesis. This work will be conducted through a combination of analytic modeling, computational modeling, and a unique cartilage explant model that completely maintains cartilage integrity and native boundary conditions such that fluid is imbibed and exuded only through the articular surface and the true impact of solute absorption can be evaluated. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.