Department of Kinesiology, Brock University, St. Catharines, ON, Canada.
Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
PLoS One. 2021 Feb 5;16(2):e0243933. doi: 10.1371/journal.pone.0243933. eCollection 2021.
Chronic low-grade inflammation has been identified as an underlying cause of many diseases including osteoporosis. Lipopolysaccharide (LPS) is a potent inducer of the inflammatory response that can negatively affect bone outcomes by upregulating bone resorption and inhibiting bone formation. The objective of this study was to assess the longitudinal response of trabecular and cortical bone structure and bone mineral density to LPS continuously administered for 12 weeks in male and female CD-1 mice. Mice were assigned to one of four LPS groups at 8-weeks of age: placebo (0.0 μg/d), low (0.9 μg/d), mid (3.6 μg/d) and high (14.4 μg/d) dose. Trabecular and cortical bone outcomes were measured at 8, 12, 16, and 20 weeks of age using in vivo micro-computed tomography. The anticipated serum LPS dose-dependent response was not observed. Therefore, the low, mid, and high LPS groups were combined for analysis. Compared to the placebo group, endpoint serum LPS was elevated in both males (p < 0.05) and females (p < 0.05) when all LPS treatment groups were combined. However, there was no significant change in trabecular or cortical bone outcomes in the combined LPS groups compared to the placebo following the 12-week LPS intervention for either sex. This suggests that although serum LPS was elevated following the 12-week LPS intervention, the dosages administered using the osmotic pumps was not sufficient to negatively impact trabecular or cortical bone outcomes in either male or female CD-1 mice.
慢性低度炎症已被确定为许多疾病的潜在原因,包括骨质疏松症。脂多糖(LPS)是炎症反应的有力诱导剂,通过上调骨吸收和抑制骨形成,对骨结局产生负面影响。本研究的目的是评估 LPS 连续给药 12 周对雄性和雌性 CD-1 小鼠的小梁和皮质骨结构及骨密度的纵向反应。8 周龄时,将小鼠分为 4 个 LPS 组之一:安慰剂(0.0μg/d)、低(0.9μg/d)、中(3.6μg/d)和高(14.4μg/d)剂量。使用体内 micro-CT 在 8、12、16 和 20 周龄时测量小梁和皮质骨结果。预期的血清 LPS 剂量依赖性反应未观察到。因此,将低、中、高 LPS 组合并进行分析。与安慰剂组相比,当合并所有 LPS 治疗组时,雄性(p<0.05)和雌性(p<0.05)的终末血清 LPS 均升高。然而,与安慰剂组相比,在 12 周 LPS 干预后,无论是雄性还是雌性,联合 LPS 组的小梁或皮质骨结果均无显著变化。这表明,尽管在 12 周 LPS 干预后血清 LPS 升高,但使用渗透泵给予的剂量不足以对雄性或雌性 CD-1 小鼠的小梁或皮质骨结果产生负面影响。