Vindoline Attenuates Osteoarthritis Progression Through Suppressing the NF-κB and ERK Pathways in Both Chondrocytes...

Area of Science:

• Pharmacology
• Biochemistry
• Orthopedics

Background:

• Osteoarthritis (OA) pathogenesis involves extracellular matrix (ECM) disruption and subchondral bone remodeling.
• Vindoline (Vin), from *Catharanthus roseus*, has anti-inflammatory effects, but its role in OA is unclear.
• Inflammation is linked to osteoclast differentiation and ECM homeostasis imbalance in OA.

Purpose of the Study:

• To investigate the effects and molecular mechanisms of Vindoline (Vin) in osteoarthritis (OA) treatment.
• To determine if Vin can suppress osteoclastogenesis and stabilize articular cartilage ECM.
• To evaluate Vin's therapeutic potential both in vitro and in vivo.

Main Methods:

• Investigated Vin's effects on RANKL-induced osteoclast formation and IL-1β-induced ECM homeostasis disorders in vitro.
• Analyzed the impact of Vin on mRNA expression of osteoclast-specific genes, catabolism, and anabolism.
• Examined Vin's inhibition of NF-κB and ERK pathways.
• Assessed Vin's protective role in destabilization of the medial meniscus (DMM)-induced OA mouse models.

Main Results:

• Vin significantly suppressed RANKL-induced osteoclast formation and stabilized IL-1β-induced ECM homeostasis disorders in a dose-dependent manner.
• Vin inhibited osteoclast-specific gene expression and IL-1β-induced catabolic markers while preserving anabolic markers.
• Vin treatment notably inhibited NF-κB and ERK pathway activation.
• In vivo studies demonstrated Vin's protective effects by reducing osteoclast formation and stabilizing cartilage ECM in OA mice.

Conclusions:

• Vindoline demonstrates significant potential for treating osteoarthritis by targeting osteoclastogenesis and ECM homeostasis.
• Vin effectively inhibits key molecular pathways, including NF-κB and ERK, involved in OA progression.
• These findings provide a molecular basis for Vin's therapeutic application in osteoarthritis management.