Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada; Restorative Dental Sciences, Faculty of Dentistry, Taibah University, Medina, Saudi Arabia.
Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada; Institute of Biomedical Engineering, University of Toronto, ON, Canada.
Dent Mater. 2023 Feb;39(2):162-169. doi: 10.1016/j.dental.2022.12.004. Epub 2023 Jan 4.
To evaluated the Odanacatib inhibitor treatment on lipopolysaccharide (LPS) contamination effect on cathepsin-K mediated dentin degradation by analysis of type I collagen C- and N-termini telopeptides.
Pulverized and disks of human dentin were demineralized and LPS contaminated, or stored in deionized water (DW) for 12 h. Samples were challenged with lactic acid (LA). Aliquots of dentin powder were treated with 1 mL Odanacatib or stored in DW for 30 min. Dentin collagen degradation was determined by sub-product release of C-terminal (ICTP and CTX) and N-terminal (NTX) telopeptides, normalized to total protein (tp) concentration (n = 3). Dentin matrix was evaluated for gravimetric (n = 8) and ultrastructural changes. Data were analyzed by Student t-test, one-way ANOVA and Tukey's test (α = 5 %).
LA incubation significantly increased telopeptide release compared with DW (p < 0.05). In untreated groups, significantly higher CTXtp, NTXtp telopeptide rates were observed for LA+LPS samples compared with DW (p < 0.01). Odanacatib significantly reduced ICTPtp, CTXtp, and NTXtp telopeptide release for LPS, LA, and LA+LPS conditions. In untreated groups, LPS and LA+LPS challenge significantly increased dentin weight loss (p = 0.02). Within each storage condition, Odanacatib treatment did not affect weight change (p > 0.05) of dentin disks.
This study showed that LPS contamination resulted in significantly higher rates of NTX than CTX from dentin matrix. Odanacatib significantly reduced telopeptide release rates of LPS contaminated dentin matrix.
通过分析 I 型胶原 C 端和 N 端肽,评估 Odanacatib 抑制剂对脂多糖(LPS)污染对组织蛋白酶-K 介导的牙本质降解的影响。
将牙本质粉末和牙本质片进行脱矿和 LPS 污染,或保存在去离子水中(DW)12 小时。将样本用乳酸(LA)进行处理。将 Odanacatib 加入到牙本质粉末的 1ml 中,或保存在 DW 中 30 分钟。通过 C 端(ICTP 和 CTX)和 N 端(NTX)肽的亚产物释放,测定牙本质胶原降解,归一化为总蛋白(tp)浓度(n=3)。对牙本质基质进行重量(n=8)和超微结构变化评估。通过学生 t 检验、单因素方差分析和 Tukey 检验(α=5%)对数据进行分析。
与 DW 相比,LA 孵育显著增加了肽的释放(p<0.05)。在未处理组中,与 DW 相比,LA+LPS 样品的 CTXtp、NTXtp 肽比率明显更高(p<0.01)。Odanacatib 显著降低了 LPS、LA 和 LA+LPS 条件下的 ICTPtp、CTXtp 和 NTXtp 肽的释放。在未处理组中,LPS 和 LA+LPS 刺激显著增加了牙本质重量损失(p=0.02)。在每种储存条件下,Odanacatib 处理都没有影响牙本质片的重量变化(p>0.05)。
本研究表明,LPS 污染导致牙本质基质中 NTX 的释放率明显高于 CTX。Odanacatib 显著降低了 LPS 污染牙本质基质的肽释放率。