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Dysregulated transforming growth factor-beta mediates early bone marrow dysfunction in diabetes

Jina J Y Kum1, Christopher J Howlett2,3,4, Zia A Khan5,6,7

  • 1Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.

Communications Biology
|October 28, 2022
PubMed

Insights

Short-term diabetes accelerates fat cell formation in bone marrow, preceding stem cell loss. This process involves suppressed transforming growth factor-beta (TGFB) signaling, offering potential therapeutic targets for diabetes.

Area of Science:

  • Biomedical Science
  • Stem Cell Biology
  • Endocrinology

Background:

  • Diabetes mellitus is known to affect multiple organs, including the eyes, kidneys, heart, and brain.
  • Previous research indicates that diabetes promotes adipogenesis (fat cell formation) in bone marrow and depletes vascular regenerative stem cells.
  • Early molecular and structural changes in the bone marrow due to diabetes remain incompletely understood.

Purpose of the Study:

  • To investigate the early, time-dependent alterations in bone marrow following the onset of diabetes.
  • To identify the molecular mechanisms underlying diabetes-induced changes in bone marrow stem cell populations.

Main Methods:

  • Spatio-temporal examination of bone marrow in a mouse model of short-term diabetes.
  • Analysis of adipogenesis and stem cell populations.
  • Investigation of transforming growth factor-beta (TGFB) signaling pathways using human bone marrow-derived mesenchymal progenitor cells.

Main Results:

  • Short-term diabetes induces significant structural and molecular changes in the bone marrow, notably enhanced adipogenesis in mouse tibiae.
  • Increased adipogenesis occurs before any observable depletion of marrow-resident stem cells.
  • Suppressed TGFB signaling was identified as a key molecular event associated with enhanced adipogenesis.

Conclusions:

  • Diabetes initiates bone marrow changes, including increased fat cell differentiation, even before stem cell depletion occurs.
  • The transforming growth factor-beta (TGFB) pathway, specifically via TGFB-activated kinase 1 (TAK1), plays a crucial role in suppressing adipogenic differentiation.
  • These findings suggest that targeting the TGFB pathway could be a therapeutic strategy to preserve stem cell function in diabetic patients.

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