Semaglutide Inhibits Osteoblast Ferroptosis Induced by Diabetic Periodontitis via Modulating the Wnt5a/Ror2/p38 MAPK...

Area of Science:

• Cell Biology
• Endocrinology
• Periodontology

Background:

• Type 2 diabetes mellitus (T2DM) exacerbates periodontitis and alveolar bone loss.
• Ferroptosis, an iron-dependent cell death, impairs osteoblasts in diabetic conditions.
• The Wnt5a/Ror2 pathway influences inflammation and bone metabolism, but its role in T2DM periodontitis is unclear.

Purpose of the Study:

• Investigate semaglutide's effects on osteoblast ferroptosis in a T2DM periodontitis model.
• Elucidate the role of the Wnt5a/Ror2/p38 MAPK pathway in semaglutide's protective mechanism.
• Evaluate semaglutide's therapeutic potential for diabetic periodontitis.

Main Methods:

• MC3T3-E1 osteoblasts were treated with high glucose and palmitic acid (HGHP) to simulate a diabetic environment.
• Osteoblast function, ferroptosis, and Wnt5a/Ror2/p38 MAPK signaling were assessed in vitro.
• T2DM mice with ligature-induced periodontitis received semaglutide treatment; alveolar bone and ferroptosis markers were analyzed in vivo.

Main Results:

• HGHP induced osteoblast ferroptosis, oxidative stress, and impaired osteogenic function.
• Semaglutide treatment restored osteoblast proliferation and function while reducing ferroptosis and oxidative stress.
• Semaglutide suppressed Wnt5a/Ror2/p38 MAPK activation; p38 inhibition negated semaglutide's benefits. In vivo, semaglutide reduced inflammation and ferroptosis in T2DM periodontitis mice.

Conclusions:

• Semaglutide mitigates ferroptosis and enhances osteogenic function in diabetic periodontitis by modulating the Wnt5a/Ror2/p38 MAPK pathway.
• These findings highlight semaglutide's potential as a therapeutic agent for T2DM-associated periodontitis.