Glycosaminoglycan chains of biglycan promote bone morphogenetic protein-4-induced osteoblast differentiation

Biglycan (BGN) has been reported to promote bone morphogenetic protein-4 (BMP-4) stimulated osteoblastic differentiation. However, the underlying mechanism has yet to be fully elucidated. The glycosaminoglycan (GAG) chains of BGN have a variety of biological functions. In the present study, we explo...

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Published in:International journal of molecular medicine 2012-11, Vol.30 (5), p.1075-1080
Main Authors: YE, YAPING, HU, WEIHUA, GUO, FENGJING, ZHANG, WEIKAI, WANG, JIANG, CHEN, ANMIN
Format: Article
Language:English
Subjects:
Adenoviruses
biglycan
bone morphogenetic protein-4
Chondroitin sulfate
Collagen
glycosaminoglycan chains
Laboratory animals
osteoblast differentiation
Phosphorylation
Proteins
Signal transduction
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Summary:Biglycan (BGN) has been reported to promote bone morphogenetic protein-4 (BMP-4) stimulated osteoblastic differentiation. However, the underlying mechanism has yet to be fully elucidated. The glycosaminoglycan (GAG) chains of BGN have a variety of biological functions. In the present study, we explored the potential role of the GAG chains of BGN in promoting BMP-4-induced osteoblast differentiation. BGN knockout (KO) murine calvarial cells were transfected with adenovirus overexpressing wild-type BGN (Adv-BGN), adenovirus expressing GAG-mutant BGN (Adv-BGNm) and adenovirus without BGN (Adv-Emp). Transfected cells were treated with or without BMP-4. Subsequently, BMP-4 signaling and function were assessed by evaluating the expression of the osteoblast differentiation-related proteins, Smad1/5/8 phosphorylation and alkaline phosphatase (ALP) activity. Furthermore, the binding specificity of the transfected cells to BMP-4 was also investigated using immunofluorescence staining. Our study demonstrated that a mutant BGN lacking GAG chains decreased BGN-assisted BMP-4 signaling and osteoblast differentiation and that the expression of this mutant BGN in biglycan knockout (BGN-KO) calvarial osteoblasts could not rescue its differ-BGN-KO) calvarial osteoblasts could not rescue its differentiation deficiency as efficiently as wild-type (WT) BGN. These results strongly suggest that the GAG chains of BGN promote BGN-assisted BMP-4 function.
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2012.1091