脂多糖（LPS）通过产生白细胞介素-1β抑制骨形态发生蛋白-2和转化生长因子-β1诱导的异位骨形成。

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

作者信息

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

机构信息

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.

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.

出版信息

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

DOI:10.1016/j.job.2020.01.004

PMID:31987892

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.

摘要

目的

为了深入了解使用骨形态发生蛋白（BMP）进行骨再生治疗期间的细菌感染情况，我们研究了脂多糖（LPS）对BMP - 2和转化生长因子（TGF）-β1诱导的小鼠异位骨形成的影响。

方法

我们将含有BMP - 2、TGF -β1和不同剂量LPS的胶原海绵植入小鼠肌肉组织。对小鼠体内形成异位骨的块状物进行微计算机断层扫描、DNA微阵列、逆转录PCR和组织学分析。

结果

LPS处理导致异位骨体积呈剂量依赖性减少。在存在LPS的情况下，BMP - 2 + TGF -β1处理诱导的异位骨总体积减少了75%以上。异位骨组织的组织学分析显示，响应LPS，总骨体积和骨体积/总体积显著减少。LPS处理显著增加了成骨细胞数量和类骨质体积，而破骨细胞数量没有变化。由于LPS诱导块状物中TNF-α和IL-1β的产生，我们将含有BMP - 2和TGF -β1且有或无LPS的胶原海绵植入TNF-α或IL-1α/β缺陷小鼠体内。LPS处理减少了TNF-α缺陷小鼠的异位骨体积，但在IL-1α/β缺陷小鼠中没有减少。此外，含有IL-1β的胶原海绵在野生型小鼠中减少BMP - 2和TGF -β1诱导的异位骨形成的程度与LPS处理相同。