The role of the angiogenesis in the endochondral occification A use of osteopetradic as mouse experimental model

软骨骨化先于血管侵入肥大软骨细胞陷窝。尽管已有文献报道破骨细胞或破软骨细胞是导致血管侵犯面横隔降解或吸收的主要原因，但仍有一些问题有待澄清。在本研究中，我们使用具有单核细胞/巨噬细胞谱系遗传缺陷的op小鼠进行形态学检查，在op小鼠的股骨或胫骨骨骺中，尽管缺乏TRAP阳性破骨细胞或破软骨细胞和F4/80阳性巨噬细胞，但其厚度和形态似乎是正常的。电镜下，在血管浸润前沿发现的细胞仅为血管内皮细胞和血管周围细胞，未观察到破骨细胞和巨噬细胞。免疫组化和电子免疫组化显示MMP-9蛋白在血管浸润前沿的细胞成分和细胞外基质中均有表达。MMP-9在同一区域的细胞中也有表达，至少部分细胞为血管内皮细胞。VEGF蛋白在骺生长板的干骺端表达较强，在肥大软骨细胞中表达较弱，提示MMP-9和VEGF诱导的血管浸润是导致肥大软骨细胞陷窝横隔破坏的主要原因，而骨细胞和巨噬细胞均不参与这一过程。

Enchondral ossification is preceded the vascular invasion into hypertrophic chondrocyte lacunae. Although it has been described that the osteoclasts or chondroclasts are primarily responsible for the degradation or resorption of the transverse septa facing to the vascular invasion front, there are some questions to be clarified. In this study, we conducted morphological aprorch using the op mouse that has an inheritent deficiency of monocyte/macrophage lineage.In the femoral or tibial epiphysis of the op mice appeared to be normal thickness and morphology despite the lack of both TRAP-positive osteoclasts or chondroclasts and F4/80 positive macrophages. Electron microscopically, the cells found in the vascular invasion front are only vascular endothelial cells and perivascular cells and neither osteoclasts nor macrophages were observed at all. This was also confirmed by the laminin immunohistochemistry as a marker for endothelial cell identification.Immunohistochemistry and electron immunohistochemistry demonstrated the expression of MMP-9 protein in both cellular component and extraoellular matric at the front of the vascular invasion. The expression of MMP-9 geen also recognized in the cells located in the same region, at least some of which were vascular endothelial cells. The expression of VEGF protein, was found intensely in the metaphysic and weakly in the hypertrophic chondrocytes in the epiphyseal growth plate.From the present study, we suggest that the vascular invasion leaded by MMP-9 and VEGF is primarily responsible for the break down of the transverse septa of hypetrophic chondrocytes lacunae and neither osteoclastic cells nor macrophages involve in this phenomenon.