State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University, Xi'an, China.
J Tissue Eng Regen Med. 2017 Oct;11(10):2922-2934. doi: 10.1002/term.2195. Epub 2016 Jul 12.
Recent studies have shown that patients with pycnodysostosis caused by cathepsin K (CTSK) genetic mutations exhibit significantly abnormal periodontal hard tissue structure. This finding suggests that CTSK may play a role in regulating the development of alveolar bone and cementum. However, the source of CTSK in the periodontal environment and the role of CTSK in periodontal regeneration, particularly hard tissue regeneration and development, remain unclear. After the isolation, cultivation, identification, and multi-lineage induction of human periodontal ligament stem cells (hPDLSCs), the present study used light and scanning electron microscopy, reverse-transcription quantitative polymerase chain reaction, western blotting, micro-computed tomography, immunohistochemical assays and ectopic hard tissue formation experiments to examine CTSK expression in hPDLSCs. The results indicated that CTSK expression was significantly upregulated in hPDLSCs during Emdogain induction but underwent minimal change during osteogenic or adipogenic induction. The present study also showed that the downregulation of CTSK expression inhibited osteogenic/cementogenic differentiation and ectopic hard tissue formation of hPDLSCs. It is therefore concluded that hPDLSCs expressed CTSK and that CTSK levels were significantly upregulated during Emdogain induction. Furthermore, CTSK promoted not only the osteogenic/cementogenic differentiation of hPDLSCs but also their ability to form ectopic hard tissue. These new findings may enhance the understanding of periodontal hard tissue development and functional regeneration. However, the specific underlying mechanisms require further investigation. Copyright © 2016 John Wiley & Sons, Ltd.
最近的研究表明，组织蛋白酶 K（CTSK）基因突变引起的先天性骨营养不良症患者表现出明显异常的牙周硬组织结构。这一发现表明 CTSK 可能在调节牙槽骨和牙骨质的发育中发挥作用。然而，牙周环境中 CTSK 的来源以及 CTSK 在牙周再生，特别是硬组织再生和发育中的作用尚不清楚。在分离、培养、鉴定和多谱系诱导人牙周膜干细胞（hPDLSCs）后，本研究使用光镜和扫描电子显微镜、反转录定量聚合酶链反应、Western blot、微计算机断层扫描、免疫组织化学检测和异位硬组织形成实验来检测 hPDLSCs 中的 CTSK 表达。结果表明，在 Emdogain 诱导过程中，hPDLSCs 中的 CTSK 表达显著上调，而在成骨或成脂诱导过程中变化很小。本研究还表明，下调 CTSK 表达抑制了 hPDLSCs 的成骨/成牙骨质分化和异位硬组织形成。因此，hPDLSCs 表达 CTSK，并且在 Emdogain 诱导过程中 CTSK 水平显著上调。此外，CTSK 不仅促进了 hPDLSCs 的成骨/成牙骨质分化，还增强了它们形成异位硬组织的能力。这些新发现可能增强对牙周硬组织发育和功能再生的理解。然而，具体的潜在机制需要进一步研究。版权所有©2016 年 John Wiley & Sons, Ltd.
