Anomalous Behavior of Hyaluronan Crosslinking Due to the Presence of Excess Phospholipids in the Articular Cartilage System of Osteoarthritis.

Wayne Augé II,Tomasz Andrysiak,Piotr Weber,Adam Gadomski,Piotr Bełdowski,Tristan De Leon,Damian Ledziński

doi:10.3390/ijms18122779

Abstract

Lubrication of articular cartilage is a complex multiscale phenomenon in synovial joint organ systems. In these systems, synovial fluid properties result from synergistic interactions between a variety of molecular constituent. Two molecular classes in particular are of importance in understanding lubrication mechanisms: hyaluronic acid and phospholipids. The purpose of this study is to evaluate interactions between hyaluronic acid and phospholipids at various functionality levels during normal and pathological synovial fluid conditions. Molecular dynamic simulations of hyaluronic acid and phospholipids complexes were performed with the concentration of hyaluronic acid set at a constant value for two organizational forms, extended (normal) and coiled (pathologic). The results demonstrated that phospholipids affect the crosslinking mechanisms of hyaluronic acid significantly and the influence is higher during pathological conditions. During normal conditions, hyaluronic acid and phospholipid interactions seem to have no competing mechanism to that of the interaction between hyaluronic acid to hyaluronic acid. On the other hand, the structures formed under pathologic conditions were highly affected by phospholipid concentration.

Highlights

Hyaluronan (HA) is a major component in many biological systems, providing functions such as modulation of fluid viscosity, surfacial lubrication, and interstitial cell-based homeostasis [1]
This study focuses on the important tribological role HA plays in synovial joint organ systems during conditions when synovial fluid phospholipids (PL) are present in excess due to pathogenesis
Without a surface active phospholipid layer, the exposed interstitial matrix remains a site of abnormal wear allowing molecular extrusion, including excess phospholipids, into the synovial fluid, constituting a reservoir which increases the biological load of intra-articular molecular debris [4]

Summary

Introduction

Hyaluronan (HA) is a major component in many biological systems, providing functions such as modulation of fluid viscosity, surfacial lubrication, and interstitial cell-based homeostasis [1]. This study focuses on the important tribological role HA plays in synovial joint organ systems during conditions when synovial fluid phospholipids (PL) are present in excess due to pathogenesis Such condition has been notably observed in the varied phenotype expressions of osteoarthritis and, along with PL molecular species adaptations, bond saturation profile shifts, and altered synovial fluid pH, have confounded clinical treatment efforts designed to normalize the intra-articular environment [2,3]. Without a surface active phospholipid layer, the exposed interstitial matrix remains a site of abnormal wear allowing molecular extrusion, including excess phospholipids, into the synovial fluid, constituting a reservoir which increases the biological load of intra-articular molecular debris [4]. Prior to enabling surgical repair of the surface active phospholipid layer, efforts to normalize the intra-articular environment had remained unsuccessful

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