Cartilage-specific deletion of ephrin-B2 in mice results in early developmental defects and an osteoarthritis-like phenotype during aging in vivo.
Arthritis Res Ther
; 18: 65, 2016 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-26980243
ABSTRACT
BACKGROUND:
Ephrins and their related receptors have been implicated in some developmental events. We have demonstrated that ephrin-B2 (EFNB2) could play a role in knee joint pathology associated with osteoarthritis (OA). Here, we delineate the in vivo role of EFNB2 in musculoskeletal growth, development, and in OA using a cartilage-specific EFNB2 knockout (EFNB2(Col2)KO) mouse model.METHODS:
EFNB2(Col2)KO was generated with Col2a1-Cre transgenic mice. The skeletal development was evaluated using macroscopy, immunohistochemistry, histomorphometry, radiology, densitometry, and micro-computed tomography. Analyses were performed at P0 (birth) and on postnatal days P15, P21, and on 8-week- and 1-year-old mice.RESULTS:
EFNB2(Col2)KO mice exhibited significant reduction in size, weight, length, and in long bones. At P0, the growth plates of EFNB2(Col2)KO mice displayed increased type X collagen, disorganized hyphertrophic zone, and decreased mineralization. At P15, mutant mice demonstrated a significant reduction in VEGF and TRAP at the chondro-osseous junction and a delay in the secondary ossification, including a decrease in bone volume and trabecular thickness. At P21 and 8 weeks old, EFNB2(Col2)KO mice exhibited reduced bone mineral density in the total skeleton, femur and spine. One-year-old EFNB2(Col2)KO mice demonstrated OA phenotypic features in both the knee and hip. By P15, 27 % of the EFNB2(Col2)KO mice developed a hip locomotor phenotype, which further experiments demonstrated reflected the neurological midline abnormality involving the corticospinal tract.CONCLUSION:
This in vivo study demonstrated, for the first time, that EFNB2 is essential for normal long bone growth and development and its absence leads to a knee and hip OA phenotype in aged mice.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
Desenvolvimento Ósseo
/
Cartilagem Articular
/
Efrina-B2
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Arthritis Res Ther
Assunto da revista:
REUMATOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Canadá