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Updated: Jan 7, 2026

Direct Mouse Trauma/Burn Model of Heterotopic Ossification
07:01

Direct Mouse Trauma/Burn Model of Heterotopic Ossification

Published on: August 6, 2015

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Carnosic acid serves as a dual Nrf2 activator and PTEN/AKT suppressor to inhibit traumatic heterotopic ossification

Donglei Wei1,2,3, Dezhi Song1,2, Hui Wang1,2

  • 1Research Centre for Regenerative Medicine, Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.

Stem Cell Research & Therapy
|December 30, 2025
PubMed
Abstract

Insights

Carnosic acid (CA) effectively treats heterotopic ossification (HO) by reducing oxidative stress and inhibiting stem cell differentiation. This natural antioxidant shows promise for HO therapy.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Regenerative Medicine

Background:

  • Heterotopic ossification (HO) is driven by reactive oxygen species (ROS) promoting stem cell differentiation.
  • Carnosic acid (CA), a natural antioxidant, has not been studied for its potential in treating HO.

Purpose of the Study:

  • To investigate the therapeutic potential of Carnosic acid (CA) in treating heterotopic ossification (HO).
  • To elucidate the mechanisms by which CA affects oxidative stress and stem cell differentiation in HO.

Main Methods:

  • In vitro studies used tendon-derived stem cells (TDSCs) stimulated with IL-1β, with CA intervention assessed via qPCR, western blotting, and immunofluorescence.
  • In vivo studies utilized a mouse model of traumatic HO induced by burn and Achilles tendon transection to evaluate CA's therapeutic effects.

Main Results:

  • CA activated the Nrf2 pathway and inhibited NOX1, reducing ROS production and antioxidant enzyme activity in vitro.
  • CA suppressed osteogenic and chondrogenic differentiation of TDSCs by regulating the PTEN/AKT pathway.
  • In vivo, CA treatment reduced HO formation by activating Nrf2, enhancing antioxidant enzymes, and inhibiting osteogenic/chondrogenic factors in Achilles tendon tissue.

Conclusions:

  • Carnosic acid (CA) presents a novel therapeutic strategy for heterotopic ossification (HO).
  • CA demonstrates dual-targeting capabilities, addressing both oxidative stress and differentiation pathways in HO pathogenesis.
Keywords:
Carnosic acidHeterotopic ossificationOsteogenic differentiationPTENReactive oxygen species

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