Daidzin Inhibits Endoplasmic Reticulum Stress by Regulating FoxO1 Expression to Alleviate Osteoarthritis Progression

Area of Science:

• Biomedical Science
• Pharmacology
• Osteoarthritis Research

Background:

• Osteoarthritis (OA) pathogenesis involves endoplasmic reticulum stress (ERS) and chondrocyte apoptosis.
• Daidzin (DDZ), a soybean-derived isoflavone, possesses known antioxidant and anti-atherosclerotic properties.
• Investigating DDZ's therapeutic potential in OA is warranted.

Purpose of the Study:

• To evaluate the therapeutic effects of Daidzin (DDZ) on osteoarthritis (OA).
• To elucidate the underlying mechanisms of Daidzin's action in OA.
• To assess DDZ in both in vivo (murine DMM model) and in vitro (TBHP-induced chondrocyte) OA models.

Main Methods:

• Established a murine Destabilization of the Medial Meniscus (DMM) model and a TBHP-induced in vitro OA chondrocyte model.
• Utilized network pharmacology to identify potential OA-related targets of Daidzin.
• Performed histological (HE, SO), imaging (X-ray, CT), and molecular analyses to assess ERS, apoptosis, ECM degradation, and FoxO1 signaling.

Main Results:

• Daidzin treatment upregulated Forkhead Box O1 (FoxO1) levels in OA models.
• Daidzin significantly inhibited endoplasmic reticulum stress (ERS) and chondrocyte apoptosis.
• Daidzin attenuated extracellular matrix (ECM) degradation in chondrocytes.

Conclusions:

• Daidzin demonstrates significant therapeutic effects in both in vivo and in vitro OA models.
• The mechanism involves upregulation of FoxO1, inhibition of ERS, and reduction of chondrocyte apoptosis and ECM degradation.
• Daidzin presents a promising therapeutic candidate for osteoarthritis treatment.