1 Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
2 Department of Oral and Maxillofacial Surgery, Fukuoka Dental College, Fukuoka, Japan.
J Dent Res. 2019 Apr;98(4):459-467. doi: 10.1177/0022034518821685. Epub 2019 Jan 9.
Ineffective oral wound healing is detrimental to patients' oral health-related quality of life. Delineating the cellular mechanisms involved in optimal healing will elicit better approaches to treating patients with compromised healing. Osteal macrophages have recently emerged as important positive regulators of bone turnover. The contributions of macrophages to long bone healing have been studied, but their role in oral osseous wound healing following tooth extraction is less clear. Clodronate-loaded liposomes were used as a tool to deplete macrophages in C57BL/6J mice and assess oral osseous bone fill after extraction. In addition to macrophage ablation, osteoclast ablation occurred. Interestingly, depletion of macrophages and osteoclasts via clodronate treatment had differential effects based on skeletal location. In the nonwounded tibiae, clodronate treatment significantly increased CD68+ cells and decreased F4/80+ cells in the marrow, which correlated with increased trabecular bone volume fraction after 7 and 14 d. Serum formation and resorptive markers P1NP and TRAcP 5b were decreased as were tibial TRAP+ osteoclasts. In healing extraction sockets, clodronate treatment increased extraction socket trabecular bone thickness at 14 d, which correlated with decreased TRAP+ osteoclasts and F4/80+ macrophages. Conversely, nonwounded maxillary interseptal bone was unaffected by clodronate treatment. Furthermore, the increase in extraction socket bone fill with clodronate was less than the large increase in trabecular bone observed in a nonwounded long bone. These data suggest a temporal and spatial specificity in the roles of macrophages and osteoclasts in normal turnover and healing.
无效的口腔伤口愈合会损害患者的口腔健康相关生活质量。阐明参与最佳愈合的细胞机制将引出更好的方法来治疗愈合受损的患者。骨巨噬细胞最近被认为是骨转换的重要正向调节因子。已经研究了巨噬细胞对长骨愈合的贡献，但它们在拔牙后口腔骨愈合中的作用尚不清楚。载有氯膦酸酯的脂质体被用作消耗 C57BL/6J 小鼠巨噬细胞的工具，并评估拔牙后口腔骨填充。除了巨噬细胞消融外，还发生了破骨细胞消融。有趣的是，通过氯膦酸盐处理消耗巨噬细胞和破骨细胞具有基于骨骼位置的差异效应。在未受伤的胫骨中，氯膦酸盐处理显著增加了骨髓中的 CD68+细胞并减少了 F4/80+细胞，这与 7 天和 14 天后小梁骨体积分数增加相关。血清形成和吸收标志物 P1NP 和 TRAcP 5b 减少，胫骨 TRAP+破骨细胞也减少。在愈合拔牙窝中，氯膦酸盐处理增加了 14 天的拔牙窝小梁骨厚度，这与 TRAP+破骨细胞和 F4/80+巨噬细胞减少相关。相反，氯膦酸盐处理对未受伤的上颌牙槽间隔骨没有影响。此外，氯膦酸盐增加拔牙窝骨填充的量小于未受伤长骨中观察到的小梁骨大量增加。这些数据表明巨噬细胞和破骨细胞在正常转换和愈合中的作用具有时间和空间特异性。
