# Therapeutic functions of tanshinone IIA in a zebrafish model of glucocorticoid-induced osteoporosis

## TL;DR

Tanshinone IIA from Salvia miltiorrhiza protects zebrafish from glucocorticoid-induced osteoporosis by improving bone and cartilage health.

## Contribution

Demonstrates TSN's osteoprotective effects in a zebrafish model of glucocorticoid-induced osteoporosis.

## Key findings

- TSN reduced glucocorticoid-induced bone loss and cartilage abnormalities in zebrafish larvae.
- Transcriptomic analysis revealed 505 genes with reversed expression, linked to skeletal development and lipid metabolism.
- Key pathways affected include PPAR signaling and fatty acid β-oxidation, with upregulated skeletal development genes.

## Abstract

Tanshinone IIA (TSN), a compound extracted from Salvia miltiorrhiza, has demonstrated a range of pharmacological activities. However, its therapeutic efficacy in glucocorticoid-induced osteoporosis (GIOP) remains insufficiently understood. This study was performed to investigate the protective effects of TSN against prednisolone (PN)-induced osteoporosis in zebrafish larvae.

The osteoprotective properties of TSN were assessed using alizarin red S staining, calcein staining, and alcian blue staining to evaluate bone mineralization, density, and cartilage development. Cardiovascular function and locomotor behavior were analyzed using transgenic zebrafish models and behavioral tracking systems. RNA sequencing was performed to identify differentially expressed genes and key signaling pathways. Protein-protein interaction networks were constructed to elucidate gene associations, and results were validated via quantitative reverse transcription polymerase chain reaction.

TSN administration effectively attenuated PN-induced developmental toxicity, enhanced bone mineralization and density, and improved cartilage abnormalities in zebrafish larvae. Transcriptomic analysis identified 505 genes with reversed expression profiles between the TSN and PN treatment groups, primarily associated with skeletal system development, lipid metabolism, and fatty acid β-oxidation. Key affected pathways included PPAR signaling, lipid atherosclerosis, and reactive oxygen species. Notably, skeletal development was characterized by the upregulation of genes including col1a1b, col2a1b, col9a3, rdh1, and acana.

These findings demonstrate the osteoprotective effects of TSN in mitigating glucocorticoid-induced bone loss and cartilage abnormalities, highlighting its potential as a therapeutic agent for GIOP. The transcriptomic insights provide novel perspectives on TSN’s role in regulating bone metabolism and skeletal development.

Infographic illustrating the anti-osteoporotic effects of TSN from Danshen on glucocorticoid-induced osteoporotic (GIOP) zebrafish. Visual elements include zebrafish skeletal diagrams, TSN chemical structure, metabolic pathways, and panels showing restored bone mineralization, physiological function, and neuroethology behavior, highlighting improvements in skeletal system development, lipid metabolism, body length, heart rate, blood flow velocity, and activity distance.