HNGF6A ameliorates oxidative stress-mediated mitochondrial dysfunction in degenerative meniscus

Area of Science:

• Biochemistry
• Cell Biology
• Orthopedics

Background:

• Meniscus injury can lead to osteoarthritis (OA) through synovitis and cartilage deterioration.
• Mitochondrial dysfunction, driven by reactive oxygen species (ROS) imbalance, is implicated in OA pathogenesis.
• The specific role of meniscal mitochondrial function in OA development requires further investigation.

Purpose of the Study:

• To investigate the protective effects of HNGF6A, a mitochondrial peptide, on meniscus senescence and degeneration.
• To elucidate the mechanisms by which HNGF6A counteracts ROS-induced OA pathogenesis.
• To assess the therapeutic potential of HNGF6A in OA treatment.

Main Methods:

• Human meniscus cells were exposed to oxidative stress (TBHP) and treated with HNGF6A.
• Mitochondrial function, ROS levels, cell apoptosis, and autophagy were assessed.
• In vivo studies involved destabilization of the medial meniscus (DMM) in mice with and without HNGF6A administration, followed by gait analysis and histological examination.

Main Results:

• HNGF6A treatment restored matrix degradation and reduced apoptosis in oxidative-stressed meniscus cells.
• HNGF6A maintained mitochondrial redox homeostasis by activating autophagy and FUNDC1.
• In vivo, HNGF6A alleviated meniscus degeneration, reduced osteophyte formation, and ameliorated OA phenotypes.

Conclusions:

• HNGF6A protects meniscus cells by restoring FUNDC1-mediated mitochondrial redox homeostasis and autophagy.
• HNGF6A demonstrates therapeutic potential for preventing and treating meniscus degeneration and OA progression.