Trabecular and cortical bone are unaltered in response to chronic lipopolysaccharide exposure via osmotic pumps in male and female CD-1 mice

Kirsten N Bott; Jenalyn L Yumol; Elena M Comelli; Panagiota Klentrou; Sandra J Peters; Wendy E Ward

doi:10.1371/journal.pone.0243933

Trabecular and cortical bone are unaltered in response to chronic lipopolysaccharide exposure via osmotic pumps in male and female CD-1 mice

PLoS One. 2021 Feb 5;16(2):e0243933. doi: 10.1371/journal.pone.0243933. eCollection 2021.

Authors

Kirsten N Bott¹, Jenalyn L Yumol¹, Elena M Comelli^{1

2

3}, Panagiota Klentrou^{1

4}, Sandra J Peters^{1

4}, Wendy E Ward^{1

2

4

5}

Affiliations

¹ Department of Kinesiology, Brock University, St. Catharines, ON, Canada.
² Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
³ Joannah and Brian Lawson Centre for Child Nutrition, University of Toronto, Toronto, ON, Canada.
⁴ Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada.
⁵ Department of Health Sciences, Brock University, St. Catharines, ON, Canada.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Density / drug effects*
Cancellous Bone / diagnostic imaging
Cancellous Bone / drug effects*
Cortical Bone / diagnostic imaging
Cortical Bone / drug effects*
Female
Lipopolysaccharides / administration & dosage*
Male
Mice
X-Ray Microtomography

Substances

Lipopolysaccharides

Grants and funding

Natural Science and Engineering Research Council Alexander Graham Bell Canada Graduate Scholarship to K.N.B. Research funding provided by Brock University and the Canada Research Chairs Program to W.E.W. (grant #230786) and a Discovery Grant from the Natural Science and Engineering Research Council to S.J.P. (grant # 229767) and W.E.W. (grant #668204). Infrastructure funding for the micro computed tomography system was provided by the Canada Foundation for Innovation to W.E.W. (grant #222084). E.M.C. holds the Lawson Family Chair in Microbiome Nutrition Research at the University of Toronto. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis,decision to publish, or preparation of the manuscript.