Reduced chondrogenic matrix accumulation by 4-methylumbelliferone reveals the potential for selective targeting of UDP-glucose dehydrogenase.
Matrix Biol
; 30(3): 163-8, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-21292001
ABSTRACT
4-Methylumbelliferone (4-MU) is described as a selective inhibitor of hyaluronan (HA) production. It is thought that 4-MU depletes UDP-glucuronic acid (UDP-GlcUA) substrate for HA synthesis and also suppresses HA-synthase expression. The possibility that 4-MU exerts at least some of its actions via regulation of UDP-glucose dehydrogenase (UGDH), a key enzyme required for both HA and sulphated-glycosaminoglycan (sGAG) production, remains unexplored. We therefore examined the effects of 4-MU on basal and retroviral UGDH-driven HA and sGAG release in cells derived from chick articular cartilage and its influence upon UGDH protein and mRNA expression and HA and sGAG production. We found that 4-MU i) suppressed UGDH mRNA and protein expression and chondrogenic matrix accumulation in chick limb bud micromass culture, ii) significantly reduced both HA and sGAG production and iii) more selectively reversed the potentiating effects of UGDH overexpression on the production of HA than sGAG. Understanding how GAG synthesis is controlled and the mechanism of 4-MU action may inform its future clinical success.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Uridina Difosfato Glucosa Deshidrogenasa
/
Himecromona
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Condrogénesis
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Matriz Extracelular
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Ácido Hialurónico
Límite:
Animals
Idioma:
En
Revista:
Matrix Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Reino Unido