# Phytol-mixed micelles alleviate dexamethasone-induced osteoporosis in zebrafish: Activation of the MMP3–OPN–MAPK pathway-mediating bone remodeling

## TL;DR

Phytol-mixed micelles help reduce osteoporosis in zebrafish by boosting bone formation and activating a key bone remodeling pathway.

## Contribution

Phytol-mixed micelles are shown to alleviate Dex-induced osteoporosis by activating the MMP3–OPN–MAPK pathway in zebrafish.

## Key findings

- Phytol increased calcium and phosphorus levels in zebrafish.
- Phytol enhanced bone formation as shown by alizarin red staining.
- Phytol upregulated ALP, TRAP, and HP, and activated the MMP3–OPN–MAPK pathway.

## Abstract

This research investigates the therapeutic efficacy of phytol-mixed micelles in mitigating dexamethasone (Dex)-induced osteoporosis in zebrafish, with a particular focus on scale regeneration. Osteoporosis was induced in zebrafish through exposure to Dex, and the effects of phytol-mixed micelles were evaluated in this model. Following phytol therapy, bone mineralization was assessed using calcium, phosphorus, and alizarin red staining tests. Additionally, commercially available kits quantified the levels of tartrate-resistant acid phosphatase (TRAP), hydroxyproline (HP), and alkaline phosphatase (ALP). The mRNA expression levels of MMP3, osteopontin (OPN), and mitogen-activated protein kinase (MAPK) were examined using reverse transcription polymerase chain reaction (RT-PCR). The findings indicated that phytol significantly increased calcium and phosphorus concentrations. Phytol-mixed micelle therapy led to increased calcium deposition and enhanced bone formation, as evidenced by alizarin red staining. Moreover, phytol administration resulted in increased HP content and upregulated ALP and TRAP activities in zebrafish. RT-PCR tests demonstrated that phytol plays a role in the restoration of the MMP3–OPN–MAPK pathway. In summary, this research highlights the potential of phytol-mixed micelles in ameliorating Dex-induced osteoporosis in zebrafish. Clarifying phytol’s mechanism, particularly its stimulation of the MMP3–OPN–MAPK pathway, provides insight into its role in facilitating bone remodeling.