Single-cell RNA sequencing reveals a distinct profile of bone immune microenvironment and decreased osteoclast differentiation in type 2 diabetic mice

Abstract

The pathogenic effects of type 2 diabetes on bone tissue are gaining attention, but the cellular and molecular mechanisms underlying osteoimmunology are still unclear in diabetes-related bone diseases. We delineated the single-cell transcriptome of bone marrow cells from both wide type and type 2 diabetes mice, which provided the first detailed global profile of bone marrow cells and revealed a distinct bone immune microenvironment at the genetic level under type 2 diabetic condition. It was observed that osteoclast activity was inhibited due to a dysregulated cytokine network, which ultimately led to decreased osteoclast formation and differentiation. In type 2 diabetes mice, a specific Cd36+ cluster (cluster 18, monocytes/macrophages 2) was identified as the precursor of osteoclasts with diminished differentiation potential. AP-1 was demonstrated to be the key transcription factor in the underlying mechanism.

Keywords

• AP-1
• Bone immune microenvironment
• Osteoclast differentiation
• Single-cell RNA sequencing
• Type 2 diabetes