Autophagy alleviates the decrease in proliferation of amyloid β1‑42‑treated bone marrow mesenchymal stem cells via...

Area of Science:

• Biomedical Science
• Cell Biology
• Gerontology

Background:

• Alzheimer's disease (AD) and osteoporosis (OP) are prevalent age-associated conditions.
• A potential link exists between AD and bone mass loss, but the underlying mechanisms are unclear.
• Amyloid-beta 1-42 (Aβ1-42), a key pathological product in AD, is investigated for its direct effects on bone cells.

Purpose of the Study:

• To determine if Aβ1-42 inhibits the proliferation of bone marrow mesenchymal stem cells (BMSCs).
• To elucidate the role of autophagy in mediating the effects of Aβ1-42 on BMSC proliferation.
• To investigate the involvement of the AKT/mTOR signaling pathway in Aβ1-42-induced changes in autophagy and BMSC proliferation.

Main Methods:

• BMSC proliferation was assessed using CCK-8 assays, cell cycle analysis, and EdU staining.
• Autophagy markers (LC3B, p62) and autophagosome formation were evaluated via Western blot, transmission electron microscopy, and immunofluorescence.
• The AKT/mTOR pathway was analyzed, and pharmacological modulators (rapamycin, 3-MA, SC79) were used to probe pathway and autophagy roles.

Main Results:

• Aβ1-42 treatment dose-dependently inhibited BMSC proliferation.
• Autophagy levels increased in BMSCs following Aβ1-42 exposure, indicating a potential compensatory response.
• The AKT/mTOR pathway was implicated in regulating autophagy, and modulating autophagy or the AKT/mTOR pathway affected Aβ1-42's impact on BMSC proliferation.

Conclusions:

• Aβ1-42 directly suppresses BMSC proliferation, independent of motor dysfunction.
• Autophagy activation serves as a resistance mechanism against Aβ1-42-induced BMSC proliferation inhibition.
• The AKT/mTOR signaling pathway plays a crucial role in regulating autophagy in response to Aβ1-42 exposure.