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RHEPARANS
Decoding role of Heparan sulfate in osteoarthritis derived-synoviocyte: simple biomarkers or main actors of senescence?
FunderFrench National Research Agency (ANR)
Funder Contribution €195,788.00
DurationFrom 01 Dec 2025
Project codeANR-25-CE44-6553
Identifiers
Description
Osteoarthritis (OA) is the most prevalent joint diseases, currently without effective treatment and associated to aging as a major risk factor. OA is due to a mechanical overload damage of the cartilage extracellular matrix (ECM), altered chondrocyte metabolism, inflammatory synovium, and more recently cellular senescence. Whereas senescence hallmarks increased during aging and associated pathology, mechanistic actors responsible for senescence during OA remain unclear and under investigations. Proteoglycans (PGs) and their glycosaminoglycan (GAG) chains are the main structural components of the joint ECM. Among these GAG, heparan sulfates (HS) exhibit complex chemical structures, with sulfation profiles that are dynamically controlled by several enzymes. These sulfation patterns play major functional roles in regulating numerous cellular properties and pathological processes. Thus, OA is characterized by significant modifications in the structure and function of HS in chondrocyte metabolism, and emerging evidence suggests that HS plays a role in cellular senescence. However, to date, no study has established a link between HS modifications and cellular senescence in an osteoarthritic context. The objective of RHEPARANS is to demonstrate that HS are biomarkers and/or key players in senescence in osteoarthritis. We hypothesize that during osteoarthritis, HS undergo structural and functional modifications associated with changes in their biosynthetic enzymes and associated PGs. The project is based on four main axes: 1) Characterize the structural alteration of HS and the expression of glycan biomarkers in senescent in vitro models of OA synoviocytes. 2) Analyze the HS sulfation profile in OA synovial membranes. This initial characterization of HS profile modifications aims to identify glycan targets of interest, whose roles in senescence will be further investigated in the subsequent tasks. 3) Determine the role of the identified glycan targets in synoviocyte senescence and identify the underlying molecular mechanisms. 4) Determine the roles/functions of HS purified from OA synovial membranes in cellular senescence. RHEPARANS project should enable us to identify new glycan based therapeutic targets for OA treatment, and to extend these results to other age-related pathologies also, such as Alzheimer's disease, as part of the emergence of this new "HS and senescence" topic in the Gly-CRRET laboratory.
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Osteoarthritis (OA) is the most prevalent joint diseases, currently without effective treatment and associated to aging as a major risk factor. OA is due to a mechanical overload damage of the cartilage extracellular matrix (ECM), altered chondrocyte metabolism, inflammatory synovium, and more recently cellular senescence. Whereas senescence hallmarks increased during aging and associated pathology, mechanistic actors responsible for senescence during OA remain unclear and under investigations. Proteoglycans (PGs) and their glycosaminoglycan (GAG) chains are the main structural components of the joint ECM. Among these GAG, heparan sulfates (HS) exhibit complex chemical structures, with sulfation profiles that are dynamically controlled by several enzymes. These sulfation patterns play major functional roles in regulating numerous cellular properties and pathological processes. Thus, OA is characterized by significant modifications in the structure and function of HS in chondrocyte metabolism, and emerging evidence suggests that HS plays a role in cellular senescence. However, to date, no study has established a link between HS modifications and cellular senescence in an osteoarthritic context. The objective of RHEPARANS is to demonstrate that HS are biomarkers and/or key players in senescence in osteoarthritis. We hypothesize that during osteoarthritis, HS undergo structural and functional modifications associated with changes in their biosynthetic enzymes and associated PGs. The project is based on four main axes: 1) Characterize the structural alteration of HS and the expression of glycan biomarkers in senescent in vitro models of OA synoviocytes. 2) Analyze the HS sulfation profile in OA synovial membranes. This initial characterization of HS profile modifications aims to identify glycan targets of interest, whose roles in senescence will be further investigated in the subsequent tasks. 3) Determine the role of the identified glycan targets in synoviocyte senescence and identify the underlying molecular mechanisms. 4) Determine the roles/functions of HS purified from OA synovial membranes in cellular senescence. RHEPARANS project should enable us to identify new glycan based therapeutic targets for OA treatment, and to extend these results to other age-related pathologies also, such as Alzheimer's disease, as part of the emergence of this new "HS and senescence" topic in the Gly-CRRET laboratory.
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Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. 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Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. 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