Zhai Yuankun, Zhou Zhuang, Xing Xiaojie, Nuzzle Mark, Zhang Xinping
Center for Musculoskeletal Research, University of Rochester, School of Medicine and Dentistry, Rochester, NY, USA.
Bone Res. 2025 Jan 13;13(1):8. doi: 10.1038/s41413-024-00379-9.
The cranial mesenchyme, originating from both neural crest and mesoderm, imparts remarkable regional specificity and complexity to postnatal calvarial tissue. While the distinct embryonic origins of the superior and dura periosteum of the cranial parietal bone have been described, the extent of their respective contributions to bone and vessel formation during adult bone defect repair remains superficially explored. Utilizing transgenic mouse models in conjunction with high-resolution multiphoton laser scanning microscopy (MPLSM), we have separately evaluated bone and vessel formation in the superior and dura periosteum before and after injury, as well as following intermittent treatment of recombinant peptide of human parathyroid hormone (rhPTH), Teriparatide. Our results show that new bone formation along the dura surface is three times greater than that along the superior periosteal surface following injury, regardless of Teriparatide treatment. Targeted deletion of PTH receptor PTH1R via SMA-CreER and Col 1a (2.3)-CreER results in selective reduction of bone formation, suggesting different progenitor cell pools in the adult superior and dura periosteum. Consistently, analyses of microvasculature show higher vessel density and better organized arterial-venous vessel network associated with a 10-fold more osteoblast clusters at dura periosteum as compared to superior periosteum. Intermittent rhPTH treatment further enhances the arterial vessel ratio at dura periosteum and type H vessel formation in cortical bone marrow space. Taken together, our study demonstrates a site-dependent coordinated osteogenic and angiogenic response, which is determined by regional osteogenic progenitor pool as well as the coupling blood vessel network at the site of cranial defect repair.
颅间充质起源于神经嵴和中胚层，赋予出生后颅骨组织显著的区域特异性和复杂性。虽然已经描述了颅顶骨上半部分和硬脑膜骨膜不同的胚胎起源，但在成人骨缺损修复过程中，它们对骨和血管形成的各自贡献程度仍有待深入研究。利用转基因小鼠模型结合高分辨率多光子激光扫描显微镜（MPLSM），我们分别评估了损伤前后以及间歇性给予人甲状旁腺激素重组肽（rhPTH）特立帕肽治疗后，上半部分和硬脑膜骨膜中的骨和血管形成情况。我们的结果表明，无论是否使用特立帕肽治疗，损伤后沿硬脑膜表面的新骨形成比沿上半部分骨膜表面的新骨形成多两倍。通过SMA-CreER和Col 1a(2.3)-CreER对甲状旁腺激素受体PTH1R进行靶向缺失，导致骨形成选择性减少，这表明在成人上半部分和硬脑膜骨膜中存在不同的祖细胞池。同样，对微血管的分析表明，与上半部分骨膜相比，硬脑膜骨膜处的血管密度更高，动静脉血管网络更有序，成骨细胞簇多10倍。间歇性rhPTH治疗进一步提高了硬脑膜骨膜处的动脉血管比例以及皮质骨髓空间中H型血管的形成。综上所述，我们的研究证明了一种位点依赖性的协调成骨和血管生成反应，这是由区域成骨祖细胞池以及颅骨缺损修复部位的耦合血管网络决定的。
