Target NF-κB p65 for preventing posttraumatic joint contracture in rats

Area of Science:

• Orthopedics
• Molecular Biology
• Regenerative Medicine

Background:

• The nuclear factor κB (NF-κB) signaling pathway, particularly the RelA/p65 subunit, plays a role in fibrotic diseases.
• The specific role of RelA/p65 in joint tissue fibrosis following traumatic injury is not well understood.

Purpose of the Study:

• To investigate the effect of inhibiting the NF-κB p65 pathway on periarticular tissue fibrosis and joint contracture after traumatic injury in a rat model.
• To determine if intra-articular p65-siRNA injection can attenuate fibroblast activation and fibrosis development.

Main Methods:

• Rats underwent knee fixation and were divided into groups receiving p65-siRNA, negative siRNA, or no intervention.
• Intra-articular injections of p65-siRNA or negative siRNA were administered.
• Assessments included X-ray for contracture, histopathology for fibrous tissue, Western blot for protein expression, and immunohistochemistry for myofibroblasts.

Main Results:

• p65-siRNA treatment significantly reduced knee flexion contracture compared to the negative siRNA group (105.7° vs. 77.73°).
• Histopathology showed decreased dense fibrous connective tissue in the p65-siRNA group.
• Western blot and immunohistochemistry revealed reduced fibrosis-related proteins and myofibroblasts in the p65-siRNA group.

Conclusions:

• Intra-articular p65-siRNA injection effectively inhibits periarticular tissue fibrosis and prevents joint contracture by downregulating the NF-κB p65 pathway.
• This method reduces fibroblast activation and fibrosis-related protein production.
• p65-siRNA represents a potential therapeutic strategy for preventing joint fibrosis after traumatic injury.