M. Mayán (A Coruña, ES)

INIBIC. A Coruña University Hospital Complex.
María Mayán is the Head of CellCOM group at INIBIC; Spain. The long-term goal of her team is to translate basic research in age-related diseases and cancer into the clinic by identifying new therapeutic targets and biomarkers. She earned her bachelor's degree in Pharmacy from University of Santiago de Compostela-Spain in 2000 and her doctoral degree from Complutense University of Madrid- Spain in 2006 (CIB; CSIC). Trained as a postdoctoral fellow at Imperial College London and at the MRC London Institute of Medical Sciences (LMS) since 2006 to 2010. She has received continuous funding from ISCIII as well as from other funding agencies and private foundations and participated in different EU Calls. She is currently PI in a coordinated grant (FET-OPEN) from the Excellent Science pillar of H2020 and in a prestigious grant with industry participation in Galicia (Biotechnology tools 4.0; 2019-2022). She is currently supervising 6 PhD students and 3 postdoctoral fellows. Dr. Mayán is an outstanding and influential researcher in the field of connexins-linked diseases. Her group has identified a novel regulator of cellular senescence; the connexin43 (Cx43); involved in inflammation; tissue remodeling and progression of age-related diseases; which also modulates EMT and participates in the activity mediated by exosomes (sEVs). Her group has discovery that chondrocytes in articular cartilage are connected by long cytoplasmic projections and cell-to-cell communication occurs via gap junctions formed by Cx43. She has demonstrated that the overactivity of Cx43 since early stages of the disease is involved in osteoarthritis (OA) progression; finding a new therapeutic target for the treatment of OA. These results have been recognized by the Spanish Society of Rheumatology (SER) with two awards in two different panels; Basic Science and Osteoarthritis. Along this line; she has published more than 11 papers in these last 8 years and registered 2 international patents with innovative therapeutic strategies based on the use of lectins and peptidomimetics to target Cx43 for the treatment of OA (PCT/US2014/045229; PCT/EP2020/071242).

Presenter Of 1 Presentation

Extended Abstract (for invited Faculty only) Osteoarthritis

1.2.1 - Role of Exosomal Connexin43 in Chondrocyte Senescence and OA Progression

Presentation Topic
Osteoarthritis
Date
12.04.2022
Lecture Time
12:00 - 12:15
Room
Potsdam 3
Session Type
Special Session

Abstract

Introduction

Role of exosomal connexin43 in chondrocyte senescence and OA progression

The accumulation of senescent cells is a key characteristic of aging, leading to the progression of age-related pathologies such as osteoarthritis (OA). Previous data from our laboratory has demonstrated that high levels of the transmembrane protein connexin43 (Cx43) are associated with a senescent phenotype in chondrocytes from osteoarthritic cartilage. OA has been reclassified as a musculoskeletal disease characterized by the breakdown of the articular cartilage affecting the whole joint, subchondral bone, synovium, ligaments, tendons and muscles. However, the mechanisms that contribute to the spread of pathogenic factors throughout the joint tissues are still unknown. Here, we show for the first time that small extracellular vesicles (sEVs) released by human OA-derived chondrocytes contain high levels of Cx43 and are able to induce a senescent phenotype in targeted chondrocytes, synovial and bone cells contributing to the formation of an inflammatory and degenerative joint environment by the secretion of senescence-associated secretory associated phenotype (SASP) molecules, including IL-1ß and IL-6 and MMPs. The enrichment of Cx43 changes the protein profile and activity of the secreted sEVs. Our results indicate a dual role for sEVs containing Cx43 inducing senescence and activating cellular plasticity in target cells mediated by NF-kß and the extracellular signal-regulated kinase 1/2 (ERK1/2), inducing epithelial-to-mesenchymal transition (EMT) signalling program and contributing to the loss of the fully differentiated phenotype. Our results demonstrated that Cx43-sEVs released by OA-derived chondrocytes spread senescence, inflammation and reprogramming factors involved in wound healing failure to neighboring tissues, contributing to the progression of the disease among cartilage, synovium, and bone and probably from one joint to another. These results highlight the importance for futures studies to consider sEVs positive for Cx43 as a new biomarker of disease progression and new target to treat OA.

Content

Role of exosomal connexin43 in chondrocyte senescence and OA progression

The accumulation of senescent cells is a key characteristic of aging, leading to the progression of age-related pathologies such as osteoarthritis (OA). Previous data from our laboratory has demonstrated that high levels of the transmembrane protein connexin43 (Cx43) are associated with a senescent phenotype in chondrocytes from osteoarthritic cartilage. OA has been reclassified as a musculoskeletal disease characterized by the breakdown of the articular cartilage affecting the whole joint, subchondral bone, synovium, ligaments, tendons and muscles. However, the mechanisms that contribute to the spread of pathogenic factors throughout the joint tissues are still unknown. Here, we show for the first time that small extracellular vesicles (sEVs) released by human OA-derived chondrocytes contain high levels of Cx43 and are able to induce a senescent phenotype in targeted chondrocytes, synovial and bone cells contributing to the formation of an inflammatory and degenerative joint environment by the secretion of senescence-associated secretory associated phenotype (SASP) molecules, including IL-1ß and IL-6 and MMPs. The enrichment of Cx43 changes the protein profile and activity of the secreted sEVs. Our results indicate a dual role for sEVs containing Cx43 inducing senescence and activating cellular plasticity in target cells mediated by NF-kß and the extracellular signal-regulated kinase 1/2 (ERK1/2), inducing epithelial-to-mesenchymal transition (EMT) signalling program and contributing to the loss of the fully differentiated phenotype. Our results demonstrated that Cx43-sEVs released by OA-derived chondrocytes spread senescence, inflammation and reprogramming factors involved in wound healing failure to neighboring tissues, contributing to the progression of the disease among cartilage, synovium, and bone and probably from one joint to another. These results highlight the importance for futures studies to consider sEVs positive for Cx43 as a new biomarker of disease progression and new target to treat OA.

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