Heparan Sulfates from Human Osteoarthritic Cartilage Display Increased Sulfation Pattern, Decrease the Protein Binding Capacity to FGF-2 and Increase the Binding to VEGF and Induce Changes of Human Mesenchymal Stem Cell Behavior

Sarah Shamdani¹, Florent Eymard^2,3, sandrine Chantepie³, Camille Flageollet¹, Nadia Henni-Chebra¹, Yoan Jouan¹, Eric Hay⁴, Martine Cohen-Solal^5,6,7,8, Dulce Papy-Garcia³, Xavier Chevalier^9,10 and Patricia Albanese¹, ¹Val de Marne, Cell Growth, Tissue Repair and Regeneration Laboratory (CRRET), UPEC EA 4397/ERL CNRS 9215, F-94000, Créteil, France, Créteil, France, ²Department of Rheumatology, APHP Henri Mondor Hospital, Creteil, France, ³Val de Marne, Cell Growth, Tissue Repair and Regeneration Laboratory (CRRET), UPEC EA 4397/ERL CNRS 9215, F-94000, Créteil, France, Creteil, France, ⁴Rheumatology Department, Lariboisiere Hospital, Inserm UMR-1132, BIOSCAR, Paris, France, ⁵Paris Diderot University, Paris, France, ⁶Rhumatologie A, INSERM U606 Hôpital Lariboisière, Centre Viggo Petersen, Paris, France, ⁷Department of rheumatology and of bone and joint imaging, hospital Lariboisiere, Paris, France, Hôpital Lariboisière, Paris, France, ⁸INSERM UMR1132, Paris Diderot University, Paris, France, ⁹94, Cell Growth, Tissue Repair and Regeneration Laboratory (CRRET), UPEC EA 4397/ERL CNRS 9215, F-94000, Créteil, France, Creteil, France, ¹⁰Rheumatology, Hopital Henri Mondor, APHP, Creteil, France

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: cartilage and osteoarthritis

Session Information

Date: Tuesday, October 23, 2018

Title: Osteoarthritis and Joint Biology – Basic Science Poster II

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

The major Glycosaminoglycan (GAGs) component of the cartilage ECM are Chondroitin Sulfates (CS) and Keratan sulfates (KS). Heparan Sulfates (HS) are also present in minority in cartilage and very few studies have been done. In general, However, HS act as central functional regulators of cell behavior, principally because of their capacities to interact with several growth factors.
Aim of this study

To characterize the quantity and degree of sulfation of the different GAGs from human normal and osteoarthritic cartilages and to look to the functional properties of HS to bind to growth factors and to induce change on mesenchymal stem cell behavior

Methods:

Human samples were harvested from osteoarhritic knee joint (different zones) after TKR and normal counterpart from femoral neck fracture. After extraction, total GAG was quantified by dimethylene blue assay and the proportion of CS, KS and HS were determined following different enzymatic treatments and were normalized to mg of dry tissue. Structure of HS and CS was determined by HPLC analysis. The capacity of the cartilage extracted GAGs to interact with heparin binding proteins such as FGF-2 and VEGF was evaluated by Elisa- based competition assay with heparin. Finally the effect of GAGs on human mesenchymal stem cell ( MSC) was evaluated on adhesion and proliferation assays

Results: 11 OA samples and 7 controlled cartilages were used. Total GAG content was decreased by1.5 fold in OA compared to normal controls. CS level was the same by KS level was decreased and level of HS decreased by 2 fold. The sulfation pattern of HS shows an increase in the % of di-sulfated disaccharides and a 2 fold decrease in non-sulfated HS. Compared to controls, OA total GAG showed a decrease affinity to FGF-2 binding (less 8 fold) and an increase affinity to VEGF (none in control). Those binding affinities were found to be mainly due to purified HS from OA compared to normal cartilages : FGF-2(2.5 fold decrease) and VEGF (3 fold increase). Interestingly in normal controlled cartilage, presence of CS/KS is able to inhibit HS binding to VEGF, while this inhibitory effect is lost in OA cartilage. Treatment with GAGs from controlled cartilage increased cell adhesion and a 30% increase in the cell numbers of MSC in a dose dependent manner. In the same concentration total GAG from OA did not induced any effect

Conclusion: For the first time, this study showed important effects of HS molecules from OA cartilage on growth factors binding and on cell behavior which may participate to the pathological processes of OA.

Disclosure: S. Shamdani, None; F. Eymard, None; S. Chantepie, None; C. Flageollet, None; N. Henni-Chebra, None; Y. Jouan, None; E. Hay, None; M. Cohen-Solal, None; D. Papy-Garcia, None; X. Chevalier, IBSA, 2, 5; P. Albanese, IBSA, 2.

To cite this abstract in AMA style:

Shamdani S, Eymard F, Chantepie S, Flageollet C, Henni-Chebra N, Jouan Y, Hay E, Cohen-Solal M, Papy-Garcia D, Chevalier X, Albanese P. Heparan Sulfates from Human Osteoarthritic Cartilage Display Increased Sulfation Pattern, Decrease the Protein Binding Capacity to FGF-2 and Increase the Binding to VEGF and Induce Changes of Human Mesenchymal Stem Cell Behavior [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/heparan-sulfates-from-human-osteoarthritic-cartilage-display-increased-sulfation-pattern-decrease-the-protein-binding-capacity-to-fgf-2-and-increase-the-binding-to-vegf-and-induce-changes-of-human-me/. Accessed .

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