Figure 6: DJ-1-deficient mice show reduced bone regeneration in a cranial critical-size defect model.

(a) Surgery was performed to induce cranial defects in wild-type (WT) and DJ-1^−/− mice (DJ-1 KO). After 3 weeks, bone defective site sections were examined by trichrome staining and photographed (X40, X100). The scale bar represents 300 μm. (b) Efficiency of bone regeneration was evaluated by measuring of the linear ingrowth of new bones from defective margins and expressed as a percentage to the total defective size. *P<0.05 versus WT. (c) Double fluorescent labels were shown at tibial cortical plate and photographed (X200). The scale bar represents 300 μm. (d) Distance between the two fluorescent labels was measured to represent the MAR (μm per day) of new bone formation. *P<0.05 versus MAR of WT. n=3 for all groups. All data are expressed as means±s.e.m. (e) Proposed mechanism for a role of DJ-1 in bone regeneration. First, DJ-1 is secreted during MSC osteogenesis. Second, secreted DJ-1 induces the migration and differentiation of endothelial cells to form functional blood vessels via activation of FGFR-1 signalling. Third, DJ-1 stimulates the osteogenesis of MSCs via FGFR-1 activation and, fourth, DJ-1 also enhances VEGF secretion during osteogenesis. Fifth, upregulation of both DJ-1 and VEGF during osteogenesis can accelerate angiogenesis at the fracture site and enhance bone regeneration.