Abstract：
OBJECTIVE: To explore the contribution of paired-related homeobox 1-positive cells to the implant-induced osseointegration process in adult alveolar bone and the potential underlying mechanisms.
METHODS: Cre recombinase-induced lineage tracing and cell ablation were conducted in a murine dental implant model. Scratch and transwell assays were used to assess MC3T3-E1 cell migration after paired-related homeobox 1 overexpression. Single-cell RNA sequencing were applied to identify potential genes involved in pairedrelated homeobox 1-positive cells-driven osteogenesis.
RESULTS: Paired-related homeobox 1- positive cells were observed to accumulate in the peri-implant area in a time-dependent manner. The number of these cells were found to reach its maximum on day 14. Osseointegration in mice were noticeably impaired after ablation of paired-related homeobox 1-positive cells. Further, it was discovered that paired-related homeobox 1 promotes MC3T3- E1 cell migration, a process which is indispensable for sound healing of peri-implant tissue. Finally, Semaphorin 3C was detected exclusively and abundantly expressed by paired-related homeobox 1-positive cells. Knockdown of semaphorin 3C in paired-related homeobox 1- positive cells significantly weakened their osteogenic potential.
CONCLUSIONS: Our data suggest that paired-related homeobox 1-positive cells contribute to the osseointegration process under stress stimulation and semaphorin 3C may play a critical role in paired-related homeobox 1- positive cell-driven osteogenesis. Paired-related homeobox 1 could significantly promote MC3T3-E1 cell migration.
METHODS: Cre recombinase-induced lineage tracing and cell ablation were conducted in a murine dental implant model. Scratch and transwell assays were used to assess MC3T3-E1 cell migration after paired-related homeobox 1 overexpression. Single-cell RNA sequencing were applied to identify potential genes involved in pairedrelated homeobox 1-positive cells-driven osteogenesis.
RESULTS: Paired-related homeobox 1- positive cells were observed to accumulate in the peri-implant area in a time-dependent manner. The number of these cells were found to reach its maximum on day 14. Osseointegration in mice were noticeably impaired after ablation of paired-related homeobox 1-positive cells. Further, it was discovered that paired-related homeobox 1 promotes MC3T3- E1 cell migration, a process which is indispensable for sound healing of peri-implant tissue. Finally, Semaphorin 3C was detected exclusively and abundantly expressed by paired-related homeobox 1-positive cells. Knockdown of semaphorin 3C in paired-related homeobox 1- positive cells significantly weakened their osteogenic potential.
CONCLUSIONS: Our data suggest that paired-related homeobox 1-positive cells contribute to the osseointegration process under stress stimulation and semaphorin 3C may play a critical role in paired-related homeobox 1- positive cell-driven osteogenesis. Paired-related homeobox 1 could significantly promote MC3T3-E1 cell migration.
摘要：
目的：探讨成对相关同源盒1阳性细胞对成人牙槽骨种植体诱导骨整合过程的贡献以及潜在的潜在机制。
方法：Cre重组酶诱导的谱系追踪和细胞消融在鼠牙种植体模型中进行。使用划痕和transwell测定来评估配对相关同源异型盒1过表达后的MC3T3-E1细胞迁移。单细胞RNA测序用于鉴定参与相关同源异型盒1阳性细胞驱动成骨的潜在基因。
结果：观察到配对相关的同源异型盒1-阳性细胞以时间依赖性方式在植入物周围区域积聚。发现这些细胞的数量在第14天达到最大值。切除配对相关的同源盒1阳性细胞后，小鼠的骨整合明显受损。Further,发现配对相关的同源异型盒1促进MC3T3-E1细胞迁移，对于种植体周围组织的声音愈合是必不可少的过程。最后,通过配对相关的同源异型框1阳性细胞专门检测并大量表达了信号蛋白3C。配对相关同源异型盒1-阳性细胞中信号素3C的敲低显着削弱了其成骨潜能。
结论：我们的数据表明，配对相关的同源盒1阳性细胞在应激刺激下促进骨整合过程，而信号素3C可能在配对相关的同源盒1阳性细胞驱动的骨形成中起关键作用。配对相关同源异型盒1能显著促进MC3T3-E1细胞的迁移。
方法：Cre重组酶诱导的谱系追踪和细胞消融在鼠牙种植体模型中进行。使用划痕和transwell测定来评估配对相关同源异型盒1过表达后的MC3T3-E1细胞迁移。单细胞RNA测序用于鉴定参与相关同源异型盒1阳性细胞驱动成骨的潜在基因。
结果：观察到配对相关的同源异型盒1-阳性细胞以时间依赖性方式在植入物周围区域积聚。发现这些细胞的数量在第14天达到最大值。切除配对相关的同源盒1阳性细胞后，小鼠的骨整合明显受损。Further,发现配对相关的同源异型盒1促进MC3T3-E1细胞迁移，对于种植体周围组织的声音愈合是必不可少的过程。最后,通过配对相关的同源异型框1阳性细胞专门检测并大量表达了信号蛋白3C。配对相关同源异型盒1-阳性细胞中信号素3C的敲低显着削弱了其成骨潜能。
结论：我们的数据表明，配对相关的同源盒1阳性细胞在应激刺激下促进骨整合过程，而信号素3C可能在配对相关的同源盒1阳性细胞驱动的骨形成中起关键作用。配对相关同源异型盒1能显著促进MC3T3-E1细胞的迁移。
