LOXL2 Deletion Triggers TMJ Osteoarthritis While Overexpression Protects Against NF-κβ-Induced Chondrocyte Apoptosis

Area of Science:

• Biochemistry
• Molecular Biology
• Orthopedics

Background:

• Temporomandibular joint osteoarthritis (TMJ-OA) is a prevalent condition with limited therapeutic options due to poorly understood molecular mechanisms.
• Lysyl Oxidase Like-2 (LOXL2) is known to protect knee cartilage and is downregulated in TMJ-OA models.

Purpose of the Study:

• To investigate the role and molecular mechanisms of LOXL2 in TMJ cartilage.
• To evaluate the therapeutic potential of LOXL2 in mitigating TMJ-OA.
• To analyze gene networks associated with LOXL2 in TMJ-OA.

Main Methods:

• Utilized in vivo Loxl2 knockout mice (Acan-Cre; Loxl2 flox/flox) and ex vivo goat TMJ cartilage.
• Analyzed gene expression, inflammatory markers, extracellular matrix (ECM) integrity, and chondrocyte apoptosis.
• Assessed the impact of LOXL2 treatment on IL-1β-induced TMJ cartilage damage.

Main Results:

• Loxl2 knockout in mice upregulated inflammatory genes (Il1b, Mmp9, Mmp13, Adamts4, Adamts5) and reduced cartilage components.
• Loxl2 deficiency was associated with enriched inflammatory response, TNFα signaling, and ECM degradation pathways.
• LOXL2 treatment reduced IL-1β-induced Mmp13 expression, protected mitochondrial function, and attenuated chondrocyte apoptosis and pain-related gene expression.

Conclusions:

• Loxl2 knockout exacerbates TMJ-OA via cartilage degradation, mitochondrial dysfunction, apoptosis, and inflammation.
• LOXL2 plays a protective role in TMJ cartilage and can mitigate TMJ-OA progression.
• LOXL2 represents a potential therapeutic target for TMJ-OA treatment.