Rosemary Extract-Induced Autophagy and Decrease in Accumulation of Collagen Type I in Osteogenesis Imperfecta Skin...

Area of Science:

• Biochemistry
• Cell Biology
• Genetics

Background:

• Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by brittle bones, primarily caused by mutations in type I collagen.
• Intracellular accumulation of mutant collagen leads to cellular stress, contributing to the disease phenotype.
• Identifying therapeutic agents that mitigate collagen accumulation and cellular stress is crucial for OI treatment.

Purpose of the Study:

• To investigate the potential of rosemary extract (RE) in reducing collagen accumulation and improving fibroblast homeostasis in patients with Osteogenesis Imperfecta.
• To explore the underlying mechanisms of RE's action, including its effects on autophagy, unfolded protein response, and apoptosis.

Main Methods:

• Fibroblast cultures from four severe/lethal OI patients were treated with varying concentrations of RE.
• Collagen accumulation levels were quantified.
• Autophagy markers (LC3-II/LC3-I ratio, p62), unfolded protein response (UPR) markers, and pro-apoptotic markers were assessed.
• Confocal microscopy was used to visualize collagen co-localization with autophagy markers (LC3-II, LAMP2A).

Main Results:

• Rosemary extract (50 and 100 µg/mL) significantly reduced accumulated type I collagen in OI fibroblasts.
• RE treatment increased the LC3-II/LC3-I ratio and decreased p62, indicating RE-induced autophagy.
• Co-localization of type I collagen with LC3-II and LAMP2A confirmed collagen degradation via autophagy.
• RE attenuated the unfolded protein response and reduced pro-apoptotic markers (Bax, CHOP, cleaved caspase 3).
• The study also explored the role of the proteasome in degrading unfolded procollagen chains.

Conclusions:

• Rosemary extract demonstrates significant potential in reducing collagen accumulation and cellular stress in Osteogenesis Imperfecta.
• RE-induced autophagy appears to be a key mechanism mediating these beneficial effects.
• These findings suggest RE could be a valuable therapeutic agent for Osteogenesis Imperfecta, targeting cellular stress pathways.