Effects of Wnt5a Haploinsufficiency on Bone Repair

Journal of orthopaedic trauma (Impact Factor: 1.8). 12/2013; 28(8). DOI: 10.1097/BOT.0000000000000041
Source: PubMed


Wnt5a expression is up-regulated during fracture repair and has previously been implicated as a potential regulator of skeletal development, as well as bone mass accrual and maintenance. Our objective was to evaluate the function of Wnt5a in fracture healing.
Femoral fracture experiments on Wnt5a and Wnt5a mice were carried out. To better understand the effect of the Wnt5a on bone repair, we evaluated radiographs using a previously validated, qualitative scoring system and performed micro-CT analyses. Histomorphometric analyses determined the temporal distribution of stroma, cartilage matrix, and woven bone in the fracture callus. Finally, we performed tartrate resistant acid phosphatase (TRAP) immunohistochemical staining to visualize and quantify bone resorbing cells.
Radiographic evaluations at day 21 demonstrated significantly higher cortical remodeling and bridging parameters for the Wnt5a group, compared to the Wnt5a group. The bone volume fraction by micro-CT was also significantly increased in Wnt5a mice. Histological and histomorphometric analyses showed that while Wnt5a mice exhibit decreased cartilage matrix production at day 7 post-fracture, they displayed increased residual cartilaginous callus at days 14 and 21, compared to the Wnt5a group. In addition, the total number of multinucleated TRAP cells was significantly lower in the Wnt5a group, than in the Wnt5a group.
The data indicates that decreased Wnt5a signaling impaired proper fracture healing, possibly through decreased cartilaginous callus formation, and delayed cartilage matrix and mineralized tissue remodeling within the fracture callus.

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