Agrin induces long-term osteochondral regeneration by supporting repair morphogenesis.
Sci Transl Med
; 12(559)2020 09 02.
Article
en En
| MEDLINE
| ID: mdl-32878982
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 ß-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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cartílago Articular
/
Agrina
Límite:
Animals
Idioma:
En
Revista:
Sci Transl Med
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2020
Tipo del documento:
Article