Paired-Related Homeobox 1-Positive Cells Are Needed for Osseointegration.

ABSTRACT

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.