4.7 Article

Liraglutide Inhibits Osteoclastogenesis and Improves Bone Loss by Downregulating Trem2 in Female Type 1 Diabetic Mice: Findings From Transcriptomics

期刊

FRONTIERS IN ENDOCRINOLOGY
卷 12, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2021.763646

关键词

type 1 diabetes; bone loss; bone density; bone microarchitecture; osteoclastogenesis; Triggering receptor expressed on myeloid cells 2; liraglutide; transcriptomics

资金

  1. National Key Research and Development Program of China [2016YFC1305000]
  2. China Diabetes Young Scientific Research Project [2018-N-01]
  3. Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019XK320031]
  4. National Natural Science Foundation of China [82100947]
  5. Science and Technology Base and Talent Project of the Guangxi Zhuang Autonomous Region, China [AD19259001]

向作者/读者索取更多资源

This study found that the bone loss in T1D mice is mainly due to increased osteoclastogenesis and upregulated expression of Trem2. Liraglutide provides protective effects on bone loss in T1D mice by suppressing osteoclastogenesis.
BackgroundThe mechanisms of bone fragility in type 1 diabetes (T1D) are not fully understood. Whether glucagon-like peptide-1 receptor (GLP-1R) agonists could improve bone quality in T1D context also remains elusive. AimsWe aimed to explore the possible mechanisms of bone loss in T1D and clarify whether liraglutide has effects on bone quality of T1D mice using transcriptomics. MethodsFemale streptozotocin-induced diabetic C57BL/6J mice were randomly divided into four groups and received the following treatments daily for 8 weeks: saline as controls, insulin, liraglutide, and liraglutide combined with insulin. These groups were also compared with non-STZ-treated normal glucose tolerance (NGT) group. Trunk blood and bone tissues were collected for analysis. Three tibia from each of the NGT, saline-treated, and liraglutide-treated groups were randomly selected for transcriptomics. ResultsCompared with NGT mice, saline-treated T1D mice manifested markedly hyperglycemia and weight loss, and micro-CT revealed significantly lower bone mineral density (BMD) and deficient microarchitectures in tibias. Eight weeks of treatment with liraglutide alone or combined with insulin rescued the decreased BMD and partly corrected the compromised trabecular microarchitectures. Transcriptomics analysis showed there were 789 differentially expressed genes mainly mapped to osteoclastogenesis and inflammation pathways. The RT-qPCR verified that the gene expression of Trem2, Nfatc1, Trap, and Ctsk were significantly increased in the tibia of T1D compared with those in the NGT group. Liraglutide treatment alone or combined with insulin could effectively suppress osteoclastogenesis by downregulating the gene expression of Trem2, Nfatc1, Ctsk, and Trap. ConclusionsTaken together, increased osteoclastogenesis with upregulated expression of Trem2 played an important role in bone loss of T1D mice. Liraglutide provided protective effects on bone loss in T1D mice by suppressing osteoclastogenesis.

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