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Related Concept Videos

Bone Disorders01:29

Bone Disorders

7.4K
Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
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Monitoring of Ubiquitin-proteasome Activity in Living Cells Using a Degron dgn-destabilized Green Fluorescent Protein GFP-based Reporter Protein
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Vesicular Galectin-3 levels decrease with donor age and contribute to the reduced osteo-inductive potential of human

Sylvia Weilner1,2, Verena Keider1, Melanie Winter1

  • 1Christian Doppler Laboratory for Biotechnology of Skin Aging, Department of Biotechnology, BOKU - University of Natural Resources and Life Sciences Vienna, 1190 Vienna, Austria.

Aging
|January 12, 2016
PubMed
Summary

Aging impairs stem cell function, reducing bone formation. Researchers found lower levels of Galectin-3 in elderly plasma extracellular vesicles, which inhibit osteogenesis. Restoring Galectin-3 enhances bone regeneration potential.

Keywords:
Galectin-3agingboneextracellular vesiclesosteogenic differentiation

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Area of Science:

  • Gerontology
  • Stem Cell Biology
  • Biochemistry

Background:

  • Aging leads to reduced physiological functions and repair capacities, partly due to impaired stem cell regeneration.
  • Osteogenic differentiation capacity (ODC) of mesenchymal stem cells (MSCs) declines with age, increasing fracture risk.
  • Systemic factors influencing age-related regenerative decline are under investigation, with a focus on plasma-derived extracellular vesicles (EVs).

Purpose of the Study:

  • To investigate the role of plasma-derived extracellular vesicles (EVs) in age-related decline of osteogenic differentiation capacity (ODC) in mesenchymal stem cells (MSCs).
  • To identify specific molecular factors within EVs that contribute to reduced ODC in the elderly.
  • To explore therapeutic strategies for enhancing ODC in aging populations.

Main Methods:

  • Comparison of osteogenic differentiation potential of MSCs treated with EVs from young versus elderly individuals.
  • Analysis of vesicular content differences, focusing on Galectin-3 levels.
  • Manipulation of Galectin-3 expression (overexpression and siRNA) and intravesicular levels in EVs.
  • Site-directed mutagenesis to identify key functional domains of Galectin-3.
  • Treatment of MSCs with cell-penetrating peptides containing a specific Galectin-3 phosphorylation site.

Main Results:

  • EVs from elderly individuals exhibited reduced osteogenic differentiation capacity compared to those from young individuals.
  • Galectin-3 levels were found to be decreased in EVs derived from the elderly.
  • Overexpression of Galectin-3 enhanced MSC osteogenesis, while its reduction impaired it.
  • Modulating intravesicular Galectin-3 levels altered the osteo-inductive potential of EVs.
  • A specific phosphorylation site on Galectin-3 was identified as crucial for its effect on ODC.
  • Cell-penetrating peptides targeting this site successfully increased ODC in MSCs.

Conclusions:

  • A decrease in plasma Galectin-3 levels contributes to the age-related decline in osteogenic differentiation capacity of MSCs.
  • Vesicular Galectin-3 plays a significant role in mediating the biological response of MSCs to EVs.
  • Targeting the Galectin-3 phosphorylation site offers a potential therapeutic strategy to improve bone regeneration in the elderly.