目的·将Cre/loxP重组酶系统与拔牙模型相结合，探究分泌Ⅰ型胶原蛋白（collagen type Ⅰ，COL1）的Col1⁺ 细胞在牙槽窝愈合过程中的时空分布规律及其向成骨细胞的分化潜能。方法·将Col1-CreERT2小鼠与Rosa26-LoxP-Stop-LoxP-tdTomato小鼠交配繁殖，以获得Col1-CreERT2；tdTomato双转基因子代小鼠。取15只子代小鼠，通过腹腔注射他莫昔芬（tamoxifen，TA）标记Col1⁺ 细胞谱系，1周后于全身麻醉下完整拔除子代小鼠右侧上颌第一磨牙，以构建双转基因小鼠拔牙模型。将子代小鼠分为5组（每组3只），分别在0、3、7、14、28 d取小鼠上颌骨样本，通过石蜡切片观察Col1⁺ 细胞谱系在牙槽窝愈合过程中的动态分布；利用免疫荧光技术标记成骨细胞特异性转录因子（osterix，OSX）、血管标志物内皮黏蛋白（endomucin，EMCN）、神经元标志物β3微管蛋白（β3-tubulin）探究Col1⁺ 细胞的成骨潜能及其与血管、神经的空间定位关系。结果·成功构建了Col1-CreERT2；tdTomato双转基因小鼠拔牙模型。石蜡切片观察的结果显示：建模后第3日，牙槽窝中出现Col1⁺细胞；第7日，Col1⁺ 细胞的数量增加，牙槽窝逐渐成骨；第28日，Col1⁺ 细胞的比例进一步上升，且分布于骨小梁周围。统计结果显示，Col1⁺ 细胞数量在牙槽窝愈合过程中随时间的推移而增加（与第0日相比，均P<0.001）。免疫荧光技术检测的结果显示，建模后第7~28日，牙槽窝内Col1⁺OSX⁺双阳性细胞数量逐渐增多，Col1⁺ 细胞在空间定位上分别与EMCN和β3-tubulin相邻。结论·在牙槽窝愈合过程中，Col1⁺ 细胞具有向成骨细胞分化的潜能，还可能参与血管、神经生成。

Objective ·To combine the Cre/loxP recombinase system with a tooth extraction model to explore the spatiotemporal distribution of Col1⁺ cells secreting type Ⅰ collagen (collagen type Ⅰ, COL1) during alveolar socket healing and their potential to differentiate into osteoblasts. Methods ·Col1-CreERT2 mice were mated with Rosa26-LoxP-Stop-LoxP-tdTomato mice to obtain Col1-CreERT2;tdTomato double transgenic offspring mice. Fifteen offspring mice were selected and tamoxifen (TA) was intraperitoneally injected to label the Col1⁺ cell lineage. One week later, the right maxillary first molars of the offspring mice were completely extracted under general anesthesia to establish a double transgenic mouse tooth extraction model. The offspring mice were divided into 5 groups, with 3 mice in each group. Maxillary bone samples were collected at 0, 3, 7, 14, and 28 days after tooth extraction, respectively. Paraffin sections were used to observe the dynamic distribution of the Col1⁺ cell lineage during alveolar socket healing. Immunofluorescence techniques were employed to label the osteoblast-specific transcription factor osterix (OSX), vascular marker endomucin (EMCN), and neuronal marker β3-tubulin to investigate the osteogenic potential of Col1⁺ cells and their spatial localization relationship with blood vessels and nerves. Results ·The tooth extraction model of Col1-CreERT2;tdTomato double transgenic mice was successfully established. Paraffin section observations revealed that Col1⁺ cells appeared in the alveolar socket on the third day after the model was established; on the seventh day, the number of Col1⁺ cells increased and alveolar socket osteogenesis gradually occurred; on the 28th day, the proportion of Col1⁺ cells further increased and they were distributed around the bone trabeculae. The results of statistical analysis showed that the number of Col1⁺ cells increased over time during alveolar socket healing (all P<0.001, compared with day 0). The results of Immunofluorescence assay indicated that the number of Col1⁺ OSX⁺ double-positive cells in the alveolar socket gradually increased from the 7th to the 28th day after the model was established, and Col1⁺ cells were spatially adjacent to EMCN and β3-tubulin. Conclusion ·During alveolar socket healing, Col1⁺ cells have the potential to differentiate into osteoblasts, and may also be involved in the formation of blood vessels and nerves.