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J Orthop Res. 2012 Feb;30(2):304-10. doi: 10.1002/jor.21505. Epub 2011 Aug 4.

Inhibition of β-catenin signaling in chondrocytes induces delayed fracture healing in mice.

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1
The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200025, China.

Abstract

Appropriate and controlled chondrogenesis and endochondral ossification play fundamental roles in the fracture healing cascade, a regenerative process involved in highly coordinated biological events, including the Wnt/β-catenin signaling pathway. To examine the role and importance of this pathway in chondrocytes, we studied bone repair of closed tibias fractures in Col2a1-ICAT transgenic mice, in which the Wnt/β-catenin signaling pathway is specially inhibited in chondrocytes. Radiological, histological, and histomorphometric analyses at 7, 9, 12, 14, 21, and 28 days after fracture demonstrated the bone repairs were retarded in Col2a1-ICAT transgenic mice, due to reduced and delayed cartilage formation, chondrocyte hypertrophy, and bone generation. In addition, at 5 weeks, Col2a1-ICAT transgenic mice exhibited a weak mechanical tolerance to four-point bending. Furthermore, quantitative-PCR analysis revealed that the expression of genes associated specifically with cartilage extracellular matrix formation (collagen II, collagen X, and mmp13), bone remodeling (alp, collagen I, and osteocalcin), and vascular extravagation (vegf), and transcriptional activators involved in cartilage generation and ossification (sox9 and runx2) was decreased and delayed in the fracture sites of Col2a1-ICAT transgenic mice during healing. Collectively, these results suggest that Wnt/β-catenin signaling is critical for fracture healing, especially with respect to chondrogenesis and endochondral ossification. Thus, our study provides insight into the possible mechanisms of and therapeutic targets for improving normal facture repair and the healing of non-union fractures.

PMID:
21818768
PMCID:
PMC3690117
DOI:
10.1002/jor.21505
[Indexed for MEDLINE]
Free PMC Article
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