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      Elastoviscous Transitions of Articular Cartilage Reveal a Mechanism of Synergy between Lubricin and Hyaluronic Acid

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          Abstract

          When lubricated by synovial fluid, articular cartilage provides some of the lowest friction coefficients found in nature. While it is known that macromolecular constituents of synovial fluid provide it with its lubricating ability, it is not fully understood how two of the main molecules, lubricin and hyaluronic acid, lubricate and interact with one another. Here, we develop a novel framework for cartilage lubrication based on the elastoviscous transition to show that lubricin and hyaluronic acid lubricate by distinct mechanisms. Such analysis revealed nonspecific interactions between these molecules in which lubricin acts to concentrate hyaluronic acid near the tissue surface and promotes a transition to a low friction regime consistent with the theory of viscous boundary lubrication. Understanding the mechanics of synovial fluid not only provides insight into the progression of diseases such as arthritis, but also may be applicable to the development of new biomimetic lubricants.

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          Most cited references30

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          Boundary lubrication of articular cartilage: role of synovial fluid constituents.

          To determine whether the synovial fluid (SF) constituents hyaluronan (HA), proteoglycan 4 (PRG4), and surface-active phospholipids (SAPL) contribute to boundary lubrication, either independently or additively, at an articular cartilage-cartilage interface. Cartilage boundary lubrication tests were performed with fresh bovine osteochondral samples. Tests were performed using graded concentrations of SF, HA, and PRG4 alone, a physiologic concentration of SAPL, and various combinations of HA, PRG4, and SAPL at physiologic concentrations. Static (mu(static, Neq)) and kinetic ( ) friction coefficients were calculated. Normal SF functioned as an effective boundary lubricant both at a concentration of 100% ( = 0.025) and at a 3-fold dilution ( = 0.029). Both HA and PRG4 contributed independently to a low mu in a dose-dependent manner. Values of decreased from approximately 0.24 in phosphate buffered saline to 0.12 in 3,300 mug/ml HA and 0.11 in 450 mug/ml PRG4. HA and PRG4 in combination lowered mu further at the high concentrations, attaining a value of 0.066. SAPL at 200 mug/ml did not significantly lower mu, either independently or in combination with HA and PRG4. The results described here indicate that SF constituents contribute, individually and in combination, both at physiologic and pathophysiologic concentrations, to the boundary lubrication of apposing articular cartilage surfaces. These results provide insight into the nature of the boundary lubrication of articular cartilage by SF and its constituents. They therefore provide insight regarding both the homeostatic maintenance of healthy joints and pathogenic processes in arthritic disease.
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            Viscosupplementation: a new concept in the treatment of osteoarthritis.

            Viscosupplementation is a new medical concept that has as its therapeutic goal the restoration of rheological homeostasis in pathological structures such as osteoarthritic joints. When the normal viscoelasticity of a solid tissue compartment or the elastoviscosity of a liquid tissue compartment is decreased under pathological conditions, normal function and regenerative processes are impaired. By introducing viscosupplementary devices, the normal rheological state of such compartments is restored or augmented. These devices stay in the tissue compartment for various periods of time, depending on the nature of the viscosupplement and the pathophysiology of the tissue compartment.
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              The role of interstitial fluid pressurization in articular cartilage lubrication.

              Over the last two decades, considerable progress has been reported in the field of cartilage mechanics that impacts our understanding of the role of interstitial fluid pressurization on cartilage lubrication. Theoretical and experimental studies have demonstrated that the interstitial fluid of cartilage pressurizes considerably under loading, potentially supporting most of the applied load under various transient or steady-state conditions. The fraction of the total load supported by fluid pressurization has been called the fluid load support. Experimental studies have demonstrated that the friction coefficient of cartilage correlates negatively with this variable, achieving remarkably low values when the fluid load support is greatest. A theoretical framework that embodies this relationship has been validated against experiments, predicting and explaining various outcomes, and demonstrating that a low friction coefficient can be maintained for prolonged loading durations under normal physiological function. This paper reviews salient aspects of this topic, as well as its implications for improving our understanding of boundary lubrication by molecular species in synovial fluid and the cartilage superficial zone. Effects of cartilage degeneration on its frictional response are also reviewed.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                24 November 2015
                2015
                : 10
                : 11
                : e0143415
                Affiliations
                [1 ]Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, United States of America
                [2 ]Department of Research and Development, Fidia Farmaceutici SpA, Padua, Italy
                [3 ]Department of Physics, Cornell University, Ithaca, NY, United States of America
                [4 ]Department of Biomedical Engineering, Cornell University, Ithaca, NY, United States of America
                University of Rochester, UNITED STATES
                Author notes

                Competing Interests: Coauthors Galesso and Secchieri are employees of Fidia Farmaceutici SpA and were involved in experimental design, material preparation, and manuscript preparation. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: EDB DG CS IC LJB. Performed the experiments: EDB. Analyzed the data: EDB LJB. Contributed reagents/materials/analysis tools: DG CS. Wrote the paper: EDB IC LJB.

                Article
                PONE-D-15-28461
                10.1371/journal.pone.0143415
                4658013
                26599797
                355ce374-6d4c-4b2b-906b-c52ca0a52f01
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 29 June 2015
                : 4 November 2015
                Page count
                Figures: 4, Tables: 0, Pages: 15
                Funding
                This project was supported by the National Science Foundation Graduate Research Fellowship Program (EDB) and Fidia Farmaceutici SpA and partially supported by the National Science Foundation under award No. DMR-1056662 (IC). Facilities and instruments used in this study were also supported by the NSF MRSEC program (DMR-1120296), and the National Institutes of Health (1S10RR025502-01). Coauthors Galesso and Secchieri are employees of Fidia Farmaceutici SpA and were involved in experimental design, material preparation, and manuscript preparation.
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