Osteoarthritis: molecular pathogenesis and potential therapeutic options

Area of Science:

• Biomedical Science
• Orthopedics
• Pharmacology

Background:

• Osteoarthritis (OA) causes chronic joint pain and inflammation, with current treatments inadequately halting disease progression.
• Pathogenesis involves complex nociceptive pathways, inflammatory mediators, and cellular organelle dysfunction, including mitochondria, lysosomes, and the endoplasmic reticulum (ER).

Purpose of the Study:

• To comprehensively review OA nociceptive pathways, bone and chondrocyte pathology, and the role of organelle dysfunction in OA pathogenesis and pain.
• To delineate emerging pharmacological strategies and advanced drug delivery systems for a multimodal therapeutic approach to OA.

Main Methods:

• Review of current literature on OA pathogenesis, focusing on nociceptive signaling, inflammation, and organelle dysfunction (mitochondria, lysosomes, ER).
• Analysis of pathological changes in bone architecture and chondrocytes, emphasizing inflammatory cytokines and organelle homeostasis.
• Exploration of novel therapeutic targets and drug delivery systems for OA treatment.

Main Results:

• OA progression is linked to mitochondrial dysfunction (ROS production, impaired ATP synthesis), lysosomal destabilization (acidification loss, apoptosis), and ER stress (cartilage degradation).
• Synergistic roles of inflammatory cytokines and organelle dysfunctions contribute to OA pathology and pain.
• Emerging strategies focus on restoring organelle homeostasis and attenuating nociceptive signaling.

Conclusions:

• Targeting organelle dysfunction (mitophagy, lysosomal integrity, ER stress alleviation) offers a multimodal therapeutic paradigm for OA.
• Advanced organelle-targeted drug delivery systems can enhance treatment efficacy and stability for OA interventions.
• These advancements provide a framework for novel OA treatments addressing both structural degeneration and clinical manifestations.