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Series GSE221936 Query DataSets for GSE221936
Status Public on May 15, 2023
Title Osteoblast-intrinsic defect in glucose metabolism impairs bone formation in type II diabetic male mice.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Skeletal fragility is associated with type 2 diabetes mellitus (T2D), but the underlying mechanism is not well understood. Here, in a mouse model for youth-onset T2D, we show that both trabecular and cortical bone mass are reduced due to diminished osteoblast activity. Stable isotope tracing in vivo with 13C-glucose demonstrates that both glycolysis and glucose fueling of the TCA cycle are impaired in diabetic bones. Similarly, Seahorse assays show suppression of both glycolysis and oxidative phosphorylation by diabetes in bone marrow mesenchymal cells as a whole, whereas single-cell RNA sequencing reveals distinct modes of metabolic dysregulation among the subpopulations. Metformin not only promotes glycolysis and osteoblast differentiation in vitro, but also improves bone mass in diabetic mice. Finally, osteoblast-specific overexpression of either Hif1a, a general inducer of glycolysis, or Pfkfb3 which stimulates a specific step in glycolysis, averts bone loss in T2D mice. The study identifies osteoblast-intrinsic defects in glucose metabolism as an underlying cause of diabetic osteopenia, which may be targeted therapeutically.
Overall design Examination of the metabolic alteration of bone marrow stromal cells (T2D vs CTRL)
Web link http://doi: 10.7554/eLife.85714.
Contributor(s) Song F, Long F
Citation(s) 37144869
Submission date Dec 30, 2022
Last update date May 17, 2023
Contact name Fanxin Long
Organization name Children's Hospital of Philadelphia
Street address Civc center blvd 3501
City Phildelphia
State/province Pennsylvania
ZIP/Postal code 19106
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM6910231 CTRL-Bone marrow stroma
GSM6910232 T2D-Bone marrow stroma
BioProject PRJNA916884

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Supplementary file Size Download File type/resource
GSE221936_RAW.tar 109.2 Mb (http)(custom) TAR (of MTX, TSV)
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Raw data are available in SRA
Processed data provided as supplementary file

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