Secreted α-Klotho maintains cartilage tissue homeostasis by repressing NOS2 and ZIP8-MMP13 catabolic axis

Paul Chuchana, Anne Laure Mausset-Bonnefont, Marc Mathieu, Francisco Espinoza, Marisa Teigell, Karine Toupet, Chantal Ripoll, Farida Djouad, Danièle Noel, Christian Jorgensen, Jean Marc Brondello*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

22 Citas (Scopus)


Progressive loss of tissue homeostasis is a hallmark of numerous age-related pathologies, including osteoarthritis (OA). Accumulation of senescent chondrocytes in joints contributes to the age-dependent cartilage loss of functions through the production of hypertrophy-associated catabolic matrix-remodeling enzymes and pro-inflammatory cytokines. Here, we evaluated the effects of the secreted variant of the antiaging hormone α-Klotho on cartilage homeostasis during both cartilage formation and OA development. First, we found that α-Klotho expression was detected during mouse limb development, and transiently expressed during in vitro chondrogenic differentiation of bone marrow-derived mesenchymal stem cells. Genome-wide gene array analysis of chondrocytes from OA patients revealed that incubation with recombinant secreted α- Klotho repressed expression of the NOS2 and ZIP8/MMP13 catabolic remodeling axis. Accordingly, α-Klotho expression was reduced in chronically IL1ß-treated chondrocytes and in cartilage of an OA mouse model. Finally, in vivo intra-articular secreted a-Kotho gene transfer delays cartilage degradation in the OA mouse model. Altogether, our results reveal a new tissue homeostatic function for this anti-aging hormone in protecting against OA onset and progression.

Idioma originalInglés
Páginas (desde-hasta)1442-1453
Número de páginas12
EstadoPublicada - 1 jun. 2018
Publicado de forma externa

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© 2018, Impact Journals LLC.


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