Department of Diagnostic and Biomedical Sciences, The University of Texas Health Science Center at Houston (UTHealth), School of Dentistry, 1941 East Road, BBS 4208, Houston, TX, 77054, USA.
Center for Craniofacial Research, The University of Texas Health Science Center at Houston, School of Dentistry, Houston, TX, 77054, USA.
Sci Rep. 2024 Mar 4;14(1):5371. doi: 10.1038/s41598-024-55998-3.
DHCR7 and SC5D are enzymes crucial for cholesterol biosynthesis, and mutations in their genes are associated with developmental disorders, which are characterized by craniofacial deformities. We have recently reported that a loss of either Dhcr7 or Sc5d results in a failure in osteoblast differentiation. However, it remains unclear to what extent a loss of function in either DHCR7 or SC5D affects craniofacial skeletal formation. Here, using micro computed tomography (μCT), we found that the bone phenotype differs in Dhcr7 and Sc5d mice in a location-specific fashion. For instance, in Sc5d mice, although craniofacial bones were overall affected, some bone segments, such as the anterior part of the premaxilla, the anterior-posterior length of the frontal bone, and the main body of the mandible, did not present significant differences compared to WT controls. By contrast, in Dhcr7 mice, while craniofacial bones were not much affected, the frontal bone was larger in width and volume, and the maxilla and palatine bone were hypoplastic, compared to WT controls. Interestingly the mandible in Dhcr7 mice was mainly affected at the condylar region, not the body. Thus, these results help us understand which bones and how greatly they are affected by cholesterol metabolism aberrations in Dhcr7 and Sc5d mice.
DHCR7 和 SC5D 是胆固醇生物合成的关键酶，其基因的突变与发育障碍有关，这些障碍的特征是颅面畸形。我们最近报道说，Dhcr7 或 Sc5d 的缺失会导致成骨细胞分化失败。然而，DHCR7 或 SC5D 的功能丧失在多大程度上影响颅面骨骼形成仍不清楚。在这里，我们使用微计算机断层扫描（μCT）发现，Dhcr7 和 Sc5d 小鼠的骨骼表型在特定部位存在差异。例如，在 Sc5d 小鼠中，尽管颅面骨骼整体受到影响，但一些骨骼片段，如前上颌骨的前部、额骨的前-后长度和下颌骨的主体，与 WT 对照组相比没有显著差异。相比之下，在 Dhcr7 小鼠中，虽然颅面骨骼没有受到太大影响，但与 WT 对照组相比，额骨在宽度和体积上更大，上颌骨和腭骨发育不良。有趣的是，Dhcr7 小鼠的下颌骨主要在髁突区域受到影响，而不是在体部。因此，这些结果帮助我们了解 Dhcr7 和 Sc5d 小鼠中胆固醇代谢异常影响哪些骨骼以及影响程度如何。
