PDF(Pubmed)
Abstract：
The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/β-Tricalcium phosphate (E-rhBMP-2/β-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/β-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/β-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/β-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ.
摘要：
药物相关性颌骨坏死（MRONJ）的病理，通常与抗再吸收治疗相关，仍然没有完全理解。已知骨细胞网络在维持骨稳态和修复中起关键作用。但是MRONJ中这些网络的确切状况是未知的。另一方面,大肠杆菌来源的重组人骨形态发生蛋白2/β-磷酸三钙（E-rhBMP-2/β-TCP）的局部应用已被证明可以促进MRONJ样小鼠模型的骨再生和减轻骨坏死，表明其在MRONJ治疗中的潜在治疗应用。然而,BMP-2治疗对恢复骨完整性的详细作用，包括它的骨细胞网络，MRONJ病情尚不清楚。因此,在本研究中，通过对MRONJ样小鼠模型的拔牙槽周围的牙槽骨应用扫描电子显微镜（SEM）分析和3D骨细胞网络重建工作流程，我们研究了BMP-2/β-TCP治疗缓解MRONJ相关骨坏死的有效性，特别关注骨细胞网络和牙槽骨微结构（微裂纹积聚）。3D骨细胞树突分析显示，与健康对照组相比，MRONJ组的骨细胞树突参数显着降低，骨重建延迟。SEM分析还显示，与健康组相比，MRONJ组的牙槽骨表面微裂纹数量显着增加。相比之下,所有这些参数在E-rhBMP-2/β-TCP治疗组中恢复至与健康组几乎相似的水平.总之,我们的研究表明，MRONJ诱导骨细胞网络降解和微裂纹积累，而E-rhBMP-2/β-TCP的应用可以恢复受损的骨细胞网络并消除MRONJ中的微裂纹积累。
