FGF8 and FGFR3 are up-regulated in hypertrophic chondrocytes: Association with chondrocyte death in deep zone of Kashin-Beck disease.
Biochem Biophys Res Commun
; 500(2): 184-190, 2018 06 02.
Article
en En
| MEDLINE
| ID: mdl-29626475
OBJECTIVE: The aim of this study was to investigate FGF8 and FGFR3 expression in clinical samples of Kashin-Beck disease (KBD), an endemic osteochondropathy found in China, as well as in pre-clinical models of this disease. METHOD: Cartilage was collected from the hand phalanges of five patients with KBD and from five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for four weeks prior to exposure to the T-2 toxin. ATDC5 cells were differentiated into hypertrophic chondrocytes for twenty-one days, and then treated with 3-morpholinosydnonimine (SIN-1) (0, 1, 3, or 5â¯mM) for 24â¯h. FGF8 and FGFR3 were visualized using immunohistochemistry; protein levels were assessed by western blotting, and mRNA levels were determined by real-time RT-PCR. RESULTS: Increased staining of FGF8 and FGFR3 was observed in the cartilage of children with KBD compared to normal children. Both increased FGF8 and FGFR3 staining, as well as protein levels, were also observed in the cartilage of rats fed normal or Se-deficient diets plus T-2 toxin exposure, compared to those in rats fed with normal or Se-deficient diets alone. SIN-1 treatment of hypertrophic chondrocytes (ATCD5 cells) increased FGF8 and FGFR3 protein and mRNA levels in a dose-dependent manner. CONCLUSION: Our data indicate that SIN-1 induces FGF8 and FGFR3 overexpression and this is involved in the abnormal terminal differentiation and degradation of the ECM in cartilage. FGF8 and FGFR3 may therefore play an important role in the onset of deep zone necrosis and pathogenesis in KBD in adolescent children.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación hacia Arriba
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Condrocitos
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Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos
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Factor 8 de Crecimiento de Fibroblastos
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Enfermedad de Kashin-Beck
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
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Child
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Child, preschool
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Humans
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Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2018
Tipo del documento:
Article
Pais de publicación:
Estados Unidos