Atypical antipsychotics induce human osteoblasts apoptosis via Wnt/β-catenin signaling

Area of Science:

• Pharmacology
• Cell Biology
• Molecular Biology

Background:

• Atypical antipsychotics (APs) are linked to increased osteoporosis risk in schizophrenia patients.
• The precise molecular mechanisms behind these osteal side effects remain unclear.
• Investigating the Wnt/β-catenin signaling pathway is crucial for understanding APs' impact on bone health.

Purpose of the Study:

• To explore the molecular mechanisms of Wnt/β-catenin signaling in atypical antipsychotic-induced osteal side effects.
• To investigate the effects of APs on osteoblast viability, apoptosis, and β-catenin expression.
• To evaluate the potential protective role of resveratrol against APs' adverse effects on bone cells.

Main Methods:

• Human osteoblast cell line (hFob1.19) were treated with olanzapine, risperidone, amisulpride, aripiprazole, or resveratrol in vitro.
• Cell viability was assessed using a cell viability assay.
• Apoptosis, apoptosis-related markers (Bcl-2, Mcl-1, Bax, Cleaved-Caspase3), and β-catenin expression were analyzed via flow cytometry, Western blot, and immunofluorescence.

Main Results:

• APs significantly decreased osteoblast proliferation and increased apoptosis rates.
• APs treatment led to reduced levels of anti-apoptotic markers (Bcl-2, Mcl-1) and increased levels of pro-apoptotic markers (Bax, Cleaved-Caspase3).
• β-catenin expression was decreased in APs-treated cells, while resveratrol co-treatment reversed apoptosis and restored β-catenin levels.

Conclusions:

• Atypical antipsychotics induce osteoblast apoptosis through the Wnt/β-catenin signaling pathway.
• Resveratrol demonstrates a protective effect, reversing AP-induced apoptosis and modulating β-catenin expression.
• These findings provide a foundation for developing strategies to overcome AP-induced bone side effects and improve patient quality of life.