Farnesol Targets the GSTP1/MAPK Axis to Inhibit Trauma-Induced Tendon Heterotopic Ossification.

Area of Science:

• Biomedical Science
• Stem Cell Biology
• Pharmacology

Background:

• Heterotopic ossification (HO) in tendons causes severe dysfunction due to abnormal differentiation of tendon-derived stem cells (TDSCs).
• Current pharmacological treatments for tendon HO are limited, necessitating novel therapeutic strategies.
• Farnesol, a natural isoprenoid, possesses anti-inflammatory properties and is a potential candidate for musculoskeletal repair.

Purpose of the Study:

• To investigate the therapeutic efficacy of Farnesol in mitigating tendon HO.
• To elucidate the molecular mechanisms underlying Farnesol's effects on TDSCs and HO.
• To assess Farnesol's potential as a novel pharmacological treatment for tendon ossification.

Main Methods:

• In vitro TDSC differentiation assays and an in vivo tendon injury model were used to evaluate Farnesol's anti-osteogenic effects.
• RNA sequencing and network pharmacology identified potential molecular targets.
• Rescue experiments with a GSTP1 inhibitor validated the mechanistic pathway.

Main Results:

• Farnesol significantly inhibited osteogenic differentiation of TDSCs in vitro.
• Farnesol treatment attenuated ectopic bone formation in the in vivo tendon injury model.
• The GSTP1/MAPK signaling axis was identified as the critical pathway, with GSTP1 being the primary mediator.

Conclusions:

• Farnesol effectively inhibits the progression of post-traumatic tendon HO.
• The mechanism involves targeting the GSTP1/MAPK pathway.
• Farnesol demonstrates therapeutic potential for preventing pathological ossification in tendons.