Isopsoralen ameliorates H₂O₂-induced damage in osteoblasts via activating the Wnt/β-catenin pathway

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• Osteoporosis is a prevalent global disease characterized by bone loss and microarchitectural deterioration, increasing fracture risk.
• Oxidative stress is implicated in the pathogenesis of osteoporosis, damaging osteoblasts and impairing bone formation.
• Understanding the molecular mechanisms underlying osteoblast protection is crucial for developing novel osteoporosis therapies.

Purpose of the Study:

• To investigate the protective effects of isopsoralen against hydrogen peroxide (H₂O₂)-induced damage in osteoblastic OB-6 cells.
• To elucidate the molecular mechanisms, particularly the Wnt/β-catenin signaling pathway, involved in isopsoralen's protective action.
• To evaluate the impact of isopsoralen on key markers of osteoblast function and oxidative stress.

Main Methods:

• Osteoblastic OB-6 cells were exposed to H₂O₂ alone or in combination with isopsoralen.
• Assays were performed to measure cell viability, apoptosis, reactive oxygen species (ROS) production, and calcium accumulation.
• Protein expression levels of key signaling molecules, including tankyrase and β-catenin, were analyzed.
• The role of the Wnt/β-catenin pathway was assessed using a tankyrase inhibitor (XAV-939).

Main Results:

• H₂O₂ treatment significantly reduced cell viability, decreased runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) expression, and inhibited calcium deposition.
• H₂O₂ exposure markedly increased osteoblast apoptosis and ROS production.
• Isopsoralen (1 µM) treatment significantly protected OB-6 cells from H₂O₂-induced damage.
• Isopsoralen upregulated the protein expression of tankyrase and β-catenin, key components of the Wnt/β-catenin pathway.
• The protective effects of isopsoralen were diminished when tankyrase activity was inhibited.

Conclusions:

• Isopsoralen demonstrates significant protective effects against oxidative stress-induced injury in osteoblasts.
• The Wnt/β-catenin signaling pathway is a critical mediator of isopsoralen's bone-protective actions.
• These findings suggest isopsoralen holds potential as a therapeutic agent for osteoporosis by combating oxidative damage in bone cells.