The NLRP3 Mediates Masticatory Muscle Atrophy by Pyroptosis and Mitophagy

Area of Science:

• Biomedical Science
• Molecular Biology
• Muscle Physiology

Background:

• Masticatory muscle atrophy impacts occlusal function, facial aesthetics, and quality of life.
• The molecular underpinnings of masticatory muscle atrophy are not well understood.
• The Nod-like receptor protein 3 (NLRP3) inflammasome is implicated in various myopathies, but its role in masticatory muscle atrophy is unclear.

Purpose of the Study:

• To investigate the role and mechanisms of NLRP3 inflammasome activation in masticatory muscle atrophy.
• To explore NLRP3 inflammasome's impact on myocyte pyroptosis, mitochondrial function, and mitophagy in muscle atrophy models.

Main Methods:

• Utilized in vivo rat models with excessive orthodontic traction to induce masticatory muscle atrophy.
• Conducted in vitro experiments on myotubes to assess NLRP3 inflammasome activation effects.
• Employed molecular and cellular assays to evaluate pyroptosis, mitochondrial integrity, and mitophagy.

Main Results:

• Excessive orthodontic traction in rats induced masticatory muscle atrophy with NLRP3 inflammasome activation and increased myocyte pyroptosis.
• Atrophied muscles showed reduced mitochondrial numbers, overactivated mitophagy, and impaired mitochondrial function.
• Inhibition of NLRP3 suppressed pyroptosis, alleviated muscle atrophy, improved mitochondrial dysfunction, and reduced excessive mitophagy.
• In vitro studies confirmed that NLRP3 knockdown mitigated pyroptosis, atrophy, mitochondrial damage, and reactive oxygen species production.

Conclusions:

• NLRP3 inflammasome activation is a key driver of masticatory muscle atrophy.
• NLRP3 induces pyroptosis, mitochondrial dysfunction, and mitophagy, contributing to muscle mass loss.
• Targeting the NLRP3 inflammasome presents a potential therapeutic strategy for masticatory muscle atrophy.