Sintered anorganic bone graft increases autocrine expression of VEGF, MMP-2 and MMP-9 during repair of critical-size bone defects

Abstract

This study aimed to evaluate morphometrically the bone formation and immunohistochemically the expression of vascular endothelial growth factor (VEGF) and metalloproteinase (MMP)-2 and -9 during the healing of critical-size defects treated with sintered anorganic bone (sAB). The 8-mm diameter full-thickness trephine defects created in the parietal bones of rats were filled with sAB (test group) or blood clot (CSD-control group). At 7, 14, 21, 30, 90 and 180 days postoperatively (n = 6/period) the volume of newly formed bone and total number of immunolabeled cells (Ntm) for each protein were determined. Bone formation was smaller and faster in the CSD-control group, stabilizing at 21 days (6.74 mm(3)). The peaks of VEGF, MMP-2 and MMP-9 occurred at 7 and 14 days in fibroblasts and osteoblasts, with mean reduction of 0.80 time at 21 days, keeping constant until 180 days. In the test group, sAB provided continuous bone formation between particles throughout all periods. The peak of MMP-2 was observed at 7-14 days in connective tissue cells and for VEGF and MMP-9 at 30 days in osteoblasts and osteocytes. Ntm for VEGF, MMP-2 and MMP-9 were in average, respectively, 3.70, 2.03 and 5.98 times higher than in the control group. At 180 days, newly formed bone (22.9 mm(3)) was 3.74 times greater in relation to control. The physical and chemical properties of sAB allow increased autocrine expression of VEGF, MMP-2 and MMP-9, favoring bone formation/remodeling with very good healing of cranial defects when compared to natural repair in the CSD-control.

DC-STAMP: A Key Regulator in Osteoclast Differentiation

“…Using video capture techniques, the trafficking of DC‐STAMP+ cells to fracture sites occurs in an organized order. Collectively, our data suggest that DC‐STAMP, together with MMP‐2 and MMP‐9 (Galliera et al, ; Rocha et al, ), can be a useful tool for monitoring, in parallel with other bone turnover markers, to evaluate bone remodeling and tissue healing. Given that DC‐STAMP+ cells are homing to bone fracture sites, a step forward approach is to molecular engineer a chimeric DC‐STAMP protein by which DC‐STAMP is able to bring small peptides/proteins such as bone morphogenetic protein 2 (BMP‐2) or MMP‐9 (Kim et al, ; Matsumoto et al, ; Miller et al, ; Saito et al, ; Wang et al, ) with healing‐promoting effects to bone fracture sites.…”

Genetic Polymorphism in MMP9 May Be Associated With Anterior Open Bite in Children

“…MMPs and TIMPs are expressed by osteoblasts (21)(22)(23)(24)(25) and play a role in bone development, modeling and remodeling. The present results demonstrated that MMP9 was associated with AOB.…”

Targeting gene expression during the early bone healing period in the mandible: A base for bone tissue engineering

“…Expression of MMP-9 was further evaluated in a critical size parietal defect in rats comparing spontaneous regeneration and application of sintered anorganic bone grafts. In the control (spontaneous healing) group, protein expression peaked in the first and second weeks after defect generation, and in the study group it M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 14 peaked at 30 days of healing (Rocha et al, 2014). It has to be taken into consideration that the defect size with regard to the critical size and the application of bone replacement material may also alter the expression on both gene and protein levels.…”