Henriquez J I, Flibotte S, Fu K, Richman J M
Department of Oral Health Sciences, University of British Columbia, Vancouver, BC, Canada.
Bioinformatics Core, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
J Dent Res. 2025 May;104(5):561-571. doi: 10.1177/00220345241304756. Epub 2025 Jan 28.
The odontoclast is a rarely studied cell type that is overly active in many dental pathologies, leading to tooth loss. It is difficult to find diphyodont mammals in which either physiological or pathological root resorption can be studied. Here we use the adult leopard gecko, which has repeated cycles of physiological tooth resorption and shedding. RNA-seq was carried out to compare gene expression profiles of functional teeth to developing teeth. Genes more highly expressed in bell-stage developing teeth were related to morphogenesis (, , , ). Some genes expressed in osteoclasts (, , ) were relatively more abundant in functional teeth compared with developing teeth. There was, however, no differential expression of RANKL () in the 2 tooth types. In addition, functional teeth expressed proteolysis genes not found in osteoclasts (, , , , , ). We used tartrate acid resistant phosphatase and cathepsin K (CTSK) staining to identify odontoclasts in and around the gecko dentition. There were 3 populations of CTSK cells: (1) large, functional multinucleated odontoclasts in the crown of the tooth with a ruffled border inside resorption pits; (2) smaller, precursor cells in the pulp with fewer nuclei; and (3) flattened external precursor cells next to the root and bone of attachment. We found a positive relationship between developing teeth and the population of CTSK+ cells on the root surface. We tested a candidate signal that may be involved in CTSK+ cell presence. An antagonist of CSF1R was delivered to developing teeth in vivo, which resulted in a significant decrease in and compared with DMSO controls. Thus, the CSF1 signaling pathway is upstream of CTSK in teeth. This is the first work to detail the molecular characteristics of odontoclasts during physiological tooth shedding and to demonstrate that in vivo, local drug delivery is possible in the gecko model.
破牙细胞是一种很少被研究的细胞类型，在许多牙齿病变中过度活跃，导致牙齿脱落。很难找到能够研究生理性或病理性牙根吸收的双牙列哺乳动物。在此，我们使用成年豹纹守宫，它具有生理性牙齿吸收和脱落的重复周期。进行RNA测序以比较功能牙与发育中牙齿的基因表达谱。在钟状期发育中牙齿中表达更高的基因与形态发生有关（……）。与发育中牙齿相比，一些在破骨细胞中表达的基因（……）在功能牙中相对更丰富。然而，两种牙齿类型中RANKL（……）没有差异表达。此外，功能牙表达了在破骨细胞中未发现的蛋白水解基因（……）。我们使用抗酒石酸酸性磷酸酶和组织蛋白酶K（CTSK）染色来鉴定守宫牙列内和周围的破牙细胞。有3种CTSK细胞群体：（1）牙齿冠部的大型、功能性多核破牙细胞，在吸收窝内有褶皱缘；（2）牙髓中较小、核较少的前体细胞；（3）附着根和骨旁边扁平的外部前体细胞。我们发现发育中牙齿与根表面CTSK+细胞群体之间存在正相关关系。我们测试了一个可能与CTSK+细胞存在有关的候选信号。将CSF1R拮抗剂体内递送至发育中牙齿，与二甲基亚砜对照组相比，导致（……）显著减少。因此，CSF1信号通路在牙齿中位于CTSK的上游。这是第一项详细描述生理性牙齿脱落过程中破牙细胞分子特征的工作，并证明在豹纹守宫模型中体内局部给药是可行的。
