Human skeletal dysplasia caused by a constitutive activated transient receptor potential vanilloid 4 (TRPV4) cation channel mutation
Experimental & Molecular Medicine
;
: 707-722, 2012.
Artículo
en Inglés
| WPRIM
| ID: wpr-110121
ABSTRACT
The transient receptor potential vanilloid 4 (TRPV4) cation channel, a member of the TRP vanilloid subfamily, is expressed in a broad range of tissues where it participates in the generation of Ca2+ signals and/or depolarization of the membrane potential. Regulation of TRPV4 abundance at the cell surface is critical for osmo- and mechanotransduction. Defects in TRPV4 are the cause of several human diseases, including brachyolmia type 3 (MIM113500) (also known as brachyrachia or spondylometaphyseal dysplasia Kozlowski type [MIM118452]), and metatropic dysplasia (MIM156530) (also called metatropic dwarfism or parastremmatic dwarfism [MIM168400]). These bone dysplasia mutants are characterized by severe dwarfism, kyphoscoliosis, distortion and bowing of the extremities, and contractures of the large joints. These diseases are characterized by a combination of decreased bone density, bowing of the long bones, platyspondyly, and striking irregularities of endochondral ossification with areas of calcific stippling and streaking in radiolucent epiphyses, metaphyses, and apophyses. In this review, we discuss the potential effect of the mutation on the regulation of TRPV4 functions, which are related to human diseases through deviated function. In particular, we emphasize how the constitutive active TRPV4 mutant affects endochondral ossification with a reduced number of hypertrophic chondrocytes and the presence of cartilage islands within the zone of primary mineralization. In addition, we summarize current knowledge about the role of TRPV4 in the pathogenesis of several diseases.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Osteocondrodisplasias
/
Osteogénesis
/
Canales Catiónicos TRPV
/
Mutación
Límite:
Humanos
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2012
Tipo del documento:
Artículo
Similares
MEDLINE
...
LILACS
LIS