Inubushi T, Kawazoe A, Miyauchi M, Yanagisawa S, Subarnbhesaj A, Chanbora C, Ayuningtyas N F, Ishikado A, Tanaka E, Takata T
Department of Oral and Maxillofacial Pathobiology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
Department of Oral and Maxillofacial Pathobiology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan; Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
Arch Oral Biol. 2014 Feb;59(2):226-32. doi: 10.1016/j.archoralbio.2013.11.002. Epub 2013 Dec 1.
Control of periodontal tissue inflammation during orthodontic treatment is very important in achieving a favourable therapeutic goal. We previously demonstrated that orally applied bovine lactoferrin (bLF) inhibited LPS-induced bone resorption but not orthodontic force-induced tooth movement in vivo. This study is designed to examine the underlying mechanism of it.
We examined the inhibitory effects of bLF on the expression of RANKL, OPG, TNF-α and COX-2 in osteoblasts loaded with compressive stress (CS) in comparison with LPS stimulated osteoblasts. Formation of osteoclasts was evaluated by co-culture system.
Both CS- and LPS-applications upregulated COX-2 and RANKL but downregulated OPG. TNF-α was upregulated in LPS-stimulated osteoblasts but downregulated in CS-loaded osteoblasts. NS398 (a specific inhibitor of COX-2) significantly inhibited CS-induced RANKL-upregulation but not LPS-induced RANKL upregulation, indicating a critical role of COX-2/PGE2 pathway in CS-induced osteoclastogenesis. bLF significantly downregulated LPS-induced upregulation of RANKL and eliminated OPG suppression but not affected in CS-induced changes. Moreover, bLF significantly decreased LPS-induced osteoclast formation, whereas bLF had no effect on PGE2-induced osteoclast formation.
bLF can effectively suppress harmful bone destruction associated with periodontitis without inhibiting bone remodelling by CS-loading. Therefore, oral administration of bLF may be highly beneficial for control of periodontitis in orthodontic patients.
在正畸治疗过程中控制牙周组织炎症对于实现良好的治疗目标非常重要。我们之前证明,口服牛乳铁蛋白(bLF)可抑制脂多糖(LPS)诱导的骨吸收,但对体内正畸力诱导的牙齿移动没有影响。本研究旨在探讨其潜在机制。
与LPS刺激的成骨细胞相比,我们检测了bLF对承受压缩应力(CS)的成骨细胞中RANKL、OPG、TNF-α和COX-2表达的抑制作用。通过共培养系统评估破骨细胞的形成。
施加CS和LPS均上调COX-2和RANKL,但下调OPG。TNF-α在LPS刺激的成骨细胞中上调,但在承受CS的成骨细胞中下调。NS398(一种COX-2特异性抑制剂)显著抑制CS诱导的RANKL上调,但不抑制LPS诱导的RANKL上调,表明COX-2/PGE2途径在CS诱导的破骨细胞生成中起关键作用。bLF显著下调LPS诱导的RANKL上调并消除OPG的抑制,但不影响CS诱导的变化。此外,bLF显著减少LPS诱导的破骨细胞形成,而bLF对PGE2诱导的破骨细胞形成没有影响。
bLF可以有效抑制与牙周炎相关的有害骨破坏,而不抑制CS加载引起的骨重塑。因此,口服bLF可能对控制正畸患者的牙周炎非常有益。