Notochordal cell matrix as a bioactive lubricant for the osteoarthritic joint

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Abstract

Notochordal cell derived matrix (NCM) can induce regenerative effects on nucleus pulposus cells and may exert such effects on chondrocytes as well. Furthermore, when dissolved at low concentrations, NCM forms a viscous fluid with potential lubricating properties. Therefore, this study tests the feasibility of the use of NCM as a regenerative lubricant for the osteoarthritic joint. Chondrocyte-seeded alginate beads were cultured in base medium (BM), BM with NCM (NCM), or BM with TGF-β1 (TGF), as well as BM and NCM treated with IL-1β. NCM increased GAG deposition and cell proliferation (stronger than TGF), and GAG/DNA ratio and hydroxyproline content (similar to TGF). These effects were maintained in the presence of IL-1β. Moreover, NCM mitigated expression of IL-1β-induced IL-6, IL-8, ADAMTS-5 and MMP-13. Reciprocating sliding friction tests of cartilage on glass were performed to test NCM’s lubricating properties relative to hyaluronic acid (HA), and showed a dose-dependent reduction in coefficient of friction with NCM, similar to HA. NCM has anabolic and anti-inflammatory effects on chondrocytes, as well as lubricating properties. Therefore, intra-articular NCM injection may have potential as a treatment to minimize pain while restoring the affected cartilage tissue in the osteoarthritic joint.

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The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration

Christine Le Maitre, Anthony J. Freemont, Judith Hoyland (2005)

In this study, we investigated the hypotheses that in human intervertebral disc (IVD) degeneration there is local production of the cytokine IL-1, and that this locally produced cytokine can induce the cellular and matrix changes of IVD degeneration. Immunohistochemistry was used to localize five members of the IL-1 family (IL-1α, IL-1β, IL-1Ra (IL-1 receptor antagonist), IL-1RI (IL-1 receptor, type I), and ICE (IL-1β-converting enzyme)) in non-degenerate and degenerate human IVDs. In addition, cells derived from non-degenerate and degenerate human IVDs were challenged with IL-1 agonists and the response was investigated using real-time PCR for a number of matrix-degrading enzymes, matrix proteins, and members of the IL-1 family. This study has shown that native disc cells from non-degenerate and degenerate discs produced the IL-1 agonists, antagonist, the active receptor, and IL-1β-converting enzyme. In addition, immunopositivity for these proteins, with the exception of IL-1Ra, increased with severity of degeneration. We have also shown that IL-1 treatment of human IVD cells resulted in increased gene expression for the matrix-degrading enzymes (MMP 3 (matrix metalloproteinase 3), MMP 13 (matrix metalloproteinase 13), and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs)) and a decrease in the gene expression for matrix genes (aggrecan, collagen II, collagen I, and SOX6). In conclusion we have shown that IL-1 is produced in the degenerate IVD. It is synthesized by native disc cells, and treatment of human disc cells with IL-1 induces an imbalance between catabolic and anabolic events, responses that represent the changes seen during disc degeneration. Therefore, inhibiting IL-1 could be an important therapeutic target for preventing and reversing disc degeneration.

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Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications.

Grigorij Kogan, Ladislav Šoltés, Robert Stern … (2006)

Hyaluronic acid (hyaluronan, HA) is a linear polysaccharide formed from disaccharide units containing N-acetyl-D-glucosamine and glucuronic acid. It has a high molecular mass, usually in the order of millions of Daltons, and interesting viscoelastic properties influenced by its polymeric and polyelectrolyte characteristics. HA is present in almost all biological fluids and tissues. In clinical medicine, it is used as a diagnostic marker for many diseases including cancer, rheumatoid arthritis and liver pathologies, as well as for supplementation of impaired synovial fluid in arthritic patients by means of intra-articular injections. It is also used in certain ophthalmological and otological surgeries and cosmetic regeneration and reconstruction of soft tissue. Herein we present an overview of the occurrence and physiological properties of HA, as well as of the recent advances in production biotechnology and preparation of the HA-based materials for medical application.

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

Thai Q. Nguyen, Petra Schumacher, Peter Schmidt … (2007)

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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Author and article information

Contributors

P. K. Sharma:

ORCID: http://orcid.org/0000-0002-8342-8939

p.k.sharma@umcg.nl

K. Ito:

ORCID: http://orcid.org/0000-0002-7372-4072

k.ito@tue.nl

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 11 June 2018

Publication date PMC-release: 11 June 2018

Publication date Collection: 2018

Volume: 8

Electronic Location Identifier: 8875

Affiliations

[1 ]ISNI 0000 0004 0398 8763, GRID grid.6852.9, Orthopaedic Biomechanics, Department of Biomedical Engineering, , Eindhoven University of Technology, ; Eindhoven, The Netherlands

[2 ]Department of Biomedical Engineering, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands

[3 ]ISNI 0000000090126352, GRID grid.7692.a, Department of Orthopaedics, , University Medical Center Utrecht, ; Utrecht, The Netherlands

Author information

P. K. Sharma http://orcid.org/0000-0002-8342-8939

K. Ito http://orcid.org/0000-0002-7372-4072

Article

Publisher ID: 27130

DOI: 10.1038/s41598-018-27130-9

PMC ID: 5995895

PubMed ID: 29891965

SO-VID: 338fb6e7-565f-4374-b112-e79caded3e01

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 20 March 2018

Date accepted : 24 May 2018

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Notochordal cell matrix as a bioactive lubricant for the osteoarthritic joint

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Most cited references 24

The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration

Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications.

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

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