Chida Suzu, Chiba Tomoki, Uchida Yutaro, Matsushima Takahide, Kurimoto Ryota, Miyazaki Takayuki, Yagasaki Lisa, Nakamura Satoshi, Mihara Emiko, Takagi Junichi, Moriyama Keiji, Asahara Hiroshi
Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan.
Department of Maxillofacial Orthognathics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-Ku, Tokyo, 113-8510, Japan.
J Bone Miner Metab. 2025 May;43(3):216-229. doi: 10.1007/s00774-025-01581-3. Epub 2025 Feb 2.
The periodontal ligament (PDL) is a structure between the alveolar bone and cementum, essential for tooth stability and composed of diverse cell types. Mohawk homeobox (Mkx) is a master transcription factor that regulates tendon and ligament homeostasis. However, the specific cell populations expressing Mkx and its role in mechanotransduction during orthodontic tooth movement (OTM) remain unclear.
We conducted single-cell RNA sequencing on wild-type rat PDL at 0 day, 1 week, and 2 weeks of post-OTM using coil springs to elucidate Mkx's function and the changes in cell populations under continuous mechanical stimulation. In addition, RT-qPCR was performed to assess the relationship between tenogenic gene expression and Mkx expression in human PDL cells.
The rat PDL was identified to consist of 14 clusters, with Mkx and Scleraxis (Scx) expressed in distinct cell populations. Collagen and ECM production increased throughout the OTM period, while the sterile inflammatory response was initially heightened and later diminished, indicating that bone remodeling occurs later in the inflammatory response. Overexpression of MKX in human PDL cells enhanced COL1A1 and DECORIN expression.
Mechanical stimulation of the PDL appears to trigger an aseptic inflammatory response that disrupts PDL homeostasis and promotes bone remodeling. Mkx may exert a protective effect on the PDL during mechanical stimulation.
牙周韧带(PDL)是牙槽骨和牙骨质之间的一种结构,对牙齿稳定性至关重要,由多种细胞类型组成。莫霍克同源框(Mkx)是一种调节肌腱和韧带稳态的主要转录因子。然而,表达Mkx的特定细胞群及其在正畸牙齿移动(OTM)过程中机械转导中的作用仍不清楚。
我们使用螺旋弹簧对OTM后0天、1周和2周的野生型大鼠PDL进行单细胞RNA测序,以阐明Mkx的功能以及在持续机械刺激下细胞群的变化。此外,进行逆转录定量聚合酶链反应(RT-qPCR)以评估人PDL细胞中肌腱生成基因表达与Mkx表达之间的关系。
大鼠PDL被鉴定为由14个细胞簇组成,Mkx和硬骨素(Scx)在不同的细胞群中表达。在整个OTM期间,胶原蛋白和细胞外基质(ECM)的产生增加,而无菌性炎症反应最初增强,随后减弱,这表明骨重塑在炎症反应后期发生。人PDL细胞中MKX的过表达增强了COL1A1和核心蛋白聚糖的表达。
对PDL的机械刺激似乎会引发无菌性炎症反应,破坏PDL稳态并促进骨重塑。Mkx可能在机械刺激期间对PDL发挥保护作用。