Isopsoralen Enhanced Osteogenesis by Targeting AhR/ERα

Area of Science:

• Pharmacology
• Cell Biology
• Bone Biology

Background:

• Isopsoralen (IPRN) from Psoralea corylifolia exhibits anti-osteoporotic effects.
• Previous studies show IPRN improves bone strength and microstructure in osteoporosis models.

Purpose of the Study:

• To investigate the molecular mechanisms of Isopsoralen-induced osteogenesis.
• To elucidate the role of aryl hydrocarbon receptor (AhR) and estrogen receptor alpha (ERα) in IPRN's osteogenic potential.

Main Methods:

• MC3T3-E1 cells were used to study IPRN's effects on osteoblast differentiation.
• Assays included calcium nodule formation, alkaline phosphatase (ALP) activity, and expression of osteoblast markers (ALP, RUNX2, COL1A1).
• Aryl hydrocarbon receptor (AhR) binding, nucleocytoplasmic shuttling, and target gene (CYP1A1) expression were analyzed. ERα expression was also assessed.

Main Results:

• IPRN promoted osteoblast differentiation, mineralization, ALP activity, and upregulated key osteoblast markers.
• IPRN directly bound to AhR, limiting its shuttling and inhibiting the AhR target gene CYP1A1.
• AhR agonists reversed the effects of IPRN, and IPRN increased ERα expression in an AhR-dependent manner.

Conclusions:

• Isopsoralen functions as an AhR antagonist.
• IPRN promotes osteoblast differentiation and mineralization through the AhR/ERα signaling pathway.
• IPRN demonstrates potential as a therapeutic agent for osteoporosis.