Juuri Emma, Tikka Pauli, Domanskyi Andrii, Corfe Ian, Morita Wataru, Mckinnon Peter J, Jandova Nela, Balic Anamaria
Cell and Tissue Dynamics Research Program, Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.
Orthodontics, Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland.
Front Physiol. 2022 Apr 28;13:877565. doi: 10.3389/fphys.2022.877565. eCollection 2022.
Ptch receptors 1 and 2 mediate Hedgehog signaling pivotal for organ development and homeostasis. In contrast to embryonic lethal phenotype, mice display no effect on gross phenotype. In this brief report, we provide evidence of changes in the putative incisor mesenchymal stem cell (MSC) niches that contribute to accelerated incisor growth, as well as intriguing changes in the bones and skin which suggest a role for Ptch2 in the regulation of MSCs and their regenerative potential. We employed histological, immunostaining, and computed tomography (µCT) analyses to analyze morphological differences between and wild-type incisors, long bones, and skins. CFU and differentiation assays were used to demonstrate the MSC content and differentiation potential of bone marrow stromal cells. Wound healing assay was performed and on 8-week-old mice to assess the effect of Ptch2 on the wound closure. Loss of causes increases in the number of putative MSCs in the continuously growing incisor, associated with increased vascularization observed in the tooth mesenchyme and the neurovascular bundle. Increased length and volume of bones is linked with the increased number and augmented differentiation potential of MSCs in the bone marrow. Dynamic changes in the skin thickness relate to changes in the mesenchymal compartment and impact the wound closure potential. The effects of abrogation on the postnatal MSCs suggest a crucial role for Ptch2 in Hedgehog signaling regulation of the organ regenerative potential.
帕奇受体1和2介导刺猬信号通路，该通路对器官发育和体内平衡至关重要。与胚胎致死表型不同，小鼠在总体表型上没有受到影响。在本简短报告中，我们提供了证据表明，假定的切牙间充质干细胞（MSC）生态位发生变化，这导致切牙生长加速，同时骨骼和皮肤也出现了有趣的变化，这表明帕奇2在调节间充质干细胞及其再生潜能中发挥作用。我们采用组织学、免疫染色和计算机断层扫描（µCT）分析来分析突变型和野生型切牙、长骨及皮肤之间的形态学差异。集落形成单位（CFU）和分化试验用于证明骨髓基质细胞的间充质干细胞含量和分化潜能。对8周龄小鼠进行伤口愈合试验，以评估帕奇2对伤口闭合的影响。帕奇2缺失导致持续生长的切牙中假定的间充质干细胞数量增加，这与在牙间充质和神经血管束中观察到的血管生成增加有关。突变型小鼠骨骼长度和体积增加与骨髓中间充质干细胞数量增加及其分化潜能增强有关。突变型小鼠皮肤厚度的动态变化与间充质成分的变化有关，并影响伤口闭合潜能。帕奇2缺失对出生后间充质干细胞的影响表明，帕奇2在刺猬信号通路对器官再生潜能的调节中起关键作用。
