Purpose: 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. Materials and 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. Conclusion: 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.