Lipopolysaccharide (LPS) inhibits ectopic bone formation induced by bone morphogenetic protein-2 and TGF-β1 through IL-1β production

Akifumi Matsumoto; Masamichi Takami; Eri Urano; Tomoya Nakamachi; Kentaro Yoshimura; Atsushi Yamada; Tetsuo Suzawa; Yoichi Miyamoto; Kazuyoshi Baba; Ryutaro Kamijo

doi:10.1016/j.job.2020.01.004

Lipopolysaccharide (LPS) inhibits ectopic bone formation induced by bone morphogenetic protein-2 and TGF-β1 through IL-1β production

J Oral Biosci. 2020 Mar;62(1):44-51. doi: 10.1016/j.job.2020.01.004. Epub 2020 Jan 24.

Authors

Affiliations

¹ Departments of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan; Departments of Prosthodontics, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan. Electronic address: [email protected].
² Departments of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan; Departments of Pharmacology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan. Electronic address: [email protected].
³ Departments of Prosthodontics, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan. Electronic address: [email protected].
⁴ Department of Anatomy, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan; Faculty of Science, Academic Assembly, University of Toyama, Japan, 3190-Gofuku, Toyama, Toyama 930-8555, Japan. Electronic address: [email protected].
⁵ Departments of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan. Electronic address: [email protected].
⁶ Departments of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan. Electronic address: [email protected].
⁷ Departments of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan. Electronic address: [email protected].
⁸ Departments of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan. Electronic address: [email protected].
⁹ Departments of Prosthodontics, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan. Electronic address: [email protected].
¹⁰ Departments of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan. Electronic address: [email protected].

PMID: 31987892
DOI: 10.1016/j.job.2020.01.004

Abstract

Objectives: In order to gain new insight into bacterial infection during bone-regenerative treatment using bone morphogenetic proteins (BMPs), we examined the effects of lipopolysaccharide (LPS) on ectopic bone formation induced by BMP-2 and transforming growth factor (TGF)-β1 in mice.

Methods: We implanted collagen sponges containing BMP-2, TGF-β1, and various amounts of LPS into mouse muscle tissues. Lump-like masses in which ectopic bones developed in mice were processed for microcomputed tomography, DNA microarray, reverse-transcription PCR, and histological analyses.

Results: LPS treatment caused a dose-dependent reduction in the volume of ectopic bone. The total volume of ectopic bone induced by BMP-2 + TGF-β1 treatment was reduced by more than 75% in the presence of LPS. Histological analysis of the ectopic bone tissues revealed a significant reduction in total bone volume and bone volume/total volume in response to LPS. LPS treatment significantly increased the osteoblast number and osteoid volume, while the osteoclast number did not change. Since LPS induced production of TNF-α and IL-1β in lump-like masses, we implanted collagen sponges containing BMP-2 and TGF-β1 with or without LPS into TNF-α- or IL-1α/β-deficient mice. LPS treatment reduced the volume of ectopic bones in TNF-α-deficient mice but not in IL-1α/β-deficient mice. Furthermore, collagen sponges containing IL-1β reduced ectopic bone formation by BMP-2 and TGF-β1 in wild-type mice to the same extent as LPS treatment did.

Conclusions: LPS suppresses the ectopic bone formation induced by BMP-2 and TGF-β1 through IL-1β production.

Keywords: Bone and bones; Bone morphogenetic proteins; Interleukin-1β; Lipopolysaccharides; Transforming growth factor β1.

Publication types

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

MeSH terms

Animals
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Interleukin-1beta
Lipopolysaccharides
Mice
Ossification, Heterotopic*
Transforming Growth Factor beta1*
X-Ray Microtomography

Substances

Bmp2 protein, mouse
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Interleukin-1beta
Lipopolysaccharides
Transforming Growth Factor beta1