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Agrin induces long-term osteochondral regeneration by supporting repair morphogenesis.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Eldridge, Suzanne E  ORCID logo  https://orcid.org/0000-0002-1630-6261
Wang, Hui 
Roelofs, Anke J 

Abstract

Cartilage loss leads to osteoarthritis, the most common cause of disability for which there is no cure. Cartilage regeneration, therefore, is a priority in medicine. We report that agrin is a potent chondrogenic factor and that a single intraarticular administration of agrin induced long-lasting regeneration of critical-size osteochondral defects in mice, with restoration of tissue architecture and bone-cartilage interface. Agrin attracted joint resident progenitor cells to the site of injury and, through simultaneous activation of CREB and suppression of canonical WNT signaling downstream of β-catenin, induced expression of the chondrogenic stem cell marker GDF5 and differentiation into stable articular chondrocytes, forming stable articular cartilage. In sheep, an agrin-containing collagen gel resulted in long-lasting regeneration of bone and cartilage, which promoted increased ambulatory activity. Our findings support the therapeutic use of agrin for joint surface regeneration.

Description

Keywords

Agrin, Animals, Cartilage, Articular, Cell Differentiation, Chondrocytes, Chondrogenesis, Mice, Sheep, Tissue Scaffolds

Journal Title

Sci Transl Med

Conference Name

Journal ISSN

1946-6234
1946-6242

Volume Title

12

Publisher

American Association for the Advancement of Science (AAAS)

Rights

All rights reserved
Sponsorship
Medical Research Council (MR/L022893/1)
Medical Research Council (MC_PC_12009)
Medical Research Council (MR/R015635/1)
Medical Research Council (MC_PC_17230)