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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2020

Open Access 01-12-2020 | Research article

Intervertebral disc degeneration in mice with type II diabetes induced by leptin receptor deficiency

Authors: Xinhua Li, Xiaoming Liu, Yiru Wang, Fuming Cao, Zhaoxiong Chen, Zhouyang Hu, Bin Yu, Hang Feng, Zhaoyu Ba, Tao Liu, Haoxi Li, Bei Jiang, Yufeng Huang, Lijun Li, Desheng Wu

Published in: BMC Musculoskeletal Disorders | Issue 1/2020

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Abstract

Background

The leptin receptor-deficient knockout (db/db) mouse is a well-established model for studying type II diabetes mellitus (T2DM). T2DM is an important risk factor of intervertebral disc degeneration (IVDD). Although the relationship between type I diabetes and IVDD has been reported by many studies, few studies have reported the effects of T2DM on IVDD in db/db mice model.

Methods

Mice were separated into 3 groups: wild-type (WT), db/db, and IGF-1 groups (leptin receptor-deficient mice were treated with insulin-like growth factor-1 (IGF-1). To observe the effects of T2DM and glucose-lowering treatment on IVDD, IGF-1 injection was used. The IVD phenotype was detected by H&E and safranin O fast green staining among db/db, WT and IGF-1 mice. The levels of blood glucose and weight in mice were also recorded. The changes in the mass of the trabecular bone in the fifth lumbar vertebra were documented by micro-computed tomography (micro-CT). Tunnel assays were used to detect cell apoptosis in each group.

Results

The weight of the mice were 27.68 ± 1.6 g in WT group, which was less than 57.56 ± 4.8 g in db/db group, and 52.17 ± 3.7 g in IGF-1 injected group (P < 0.05). The blood glucose levels were also significantly higher in the db/db mice group. T2DM caused by leptin receptor knockout showed an association with significantly decreased vertebral bone mass and increased IVDD when compared to WT mice. The db/db mice induced by leptin deletion showed a higher percentage of MMP3 expression as well as cell apoptosis in IVDD mice than WT mice (P < 0.05), while IGF-1 treatment reversed this situation (P < 0.05).

Conclusions

T2DM induced by leptin receptor knockout led to IVDD by increasing the levels of MMP3 and promoting cell apoptosis. IGF-1 treatment partially rescue the phenotype of IVDD induced by leptin receptor knockout.
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Metadata
Title
Intervertebral disc degeneration in mice with type II diabetes induced by leptin receptor deficiency
Authors
Xinhua Li
Xiaoming Liu
Yiru Wang
Fuming Cao
Zhaoxiong Chen
Zhouyang Hu
Bin Yu
Hang Feng
Zhaoyu Ba
Tao Liu
Haoxi Li
Bei Jiang
Yufeng Huang
Lijun Li
Desheng Wu
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2020
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-020-3091-1

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