Heparan sulfate functions are altered in the osteoarthritic cartilage
- PDF / 1,475,021 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 2 Downloads / 205 Views
(2020) 22:283
RESEARCH ARTICLE
Open Access
Heparan sulfate functions are altered in the osteoarthritic cartilage Sara Shamdani1, Sandrine Chantepie1, Camille Flageollet1, Nadia Henni-Chebra1, Yohann Jouan2,3, Florent Eymard1,4, Eric Hay2,3, Martine Cohen-Solal5,2,3, Dulce Papy-Garcia1, Xavier Chevalier1,4 and Patricia Albanese1*
Abstract Background: Heparan sulfate (HS) proteoglycans (PG) may be found at the chondrocyte surface and in the pericellular cartilage matrix, and are involved in cell-cell and cell-matrix interactions. An important function of HS chains is to regulate cell fate through specific interactions with heparin-binding proteins (HBP) modulated by their complex sulfation pattern. Osteoarthritis (OA) is a joint disorder characterized by the degradation of articular cartilaginous extracellular matrix. The aim of this study was to investigate HS structure and functions in osteoarthritic cartilages compared to normal cartilages (controls). Methods: Glycosaminoglycans (GAG) were extracted from human macroscopically normal cartilages (controls, n = 7) and (OA cartilages n = 11). HS were isolated and quantified using the DMMB quantification method. Their structure and functions were then compared using respectively a HPLC analysis and HBP binding tests and their phenotypic effects on murine chondrocytes were studied by RQ-PCR. Statistical analyzes were performed using a one-way ANOVA followed by a Dunnett’s test or a t test for pairwise comparisons. Results: In OA, HS were characterized by increased sulfation levels compared to controls. Moreover, the capacity of these HS to bind HBP involved in the OA pathophysiological process such as FGF2 and VEGF was reduced. Chondroitin sulfates and keratan sulfates regulated these binding properties. Finally, HS from OA cartilages induced the mRNA levels of catabolic markers such as MMP3, MMP13, and TS4 and inhibited the mRNA levels of anabolic markers such as COL2, ACAN, SOX9, and VEGF in murine articular chondrocytes. Conclusion: The sulfation of HS chains was increased in OA cartilages with changes in HBP binding properties and biological effects on chondrocyte phenotypes. Thus, modified HS present in altered cartilages could be a novel therapeutic target in OA. Keywords: Heparan sulfate, Sulfation, Osteoarthritis, Cartilage matrix, Chondrocytes
* Correspondence: [email protected] 1 Univ Paris Est Creteil, Gly-CRRET, Glycobiology Cell Growth Tissue Repair and Regeneration Research Unit, Créteil F-94010, France Full list of author information is available at the end of the article
© The Author(s). 2020 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons
Data Loading...
