Insights into potential multi-target protective effects of Tanshinone IIA in steroid-induced osteonecrosis of the femoral head: evidence from integrated metabolomics and proteomics
5 affiliations
- 1First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine
- 2Department of General Medicine, The 960th Hospital of the PLA Joint Logistic Support Force
- 3College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine
- 4Orthopaedic Microsurgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine
- 5The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine
Abstract
Objective: To systematically evaluate the interventional effects of Tanshinone IIA on a rat model of steroid-induced osteonecrosis of the femoral head (SONFH) based on metabolomics and proteomics technologies, and to elucidate its multi-target regulatory mechanisms.
Methods: Twenty-four SD rats were randomly divided into a Control group, a model group, and a Tanshinone IIA group, with eight rats in each group. Micro-CT, HE staining, and TRAP staining were used to assess the bone microarchitecture and pathological changes of the femoral head. UPLC-MS/MS-based untargeted metabolomics combined with DIA quantitative proteomics were employed to analyze the metabolite and protein expression profiles of fecal and femoral head samples. Differential metabolites and differentially expressed proteins were screened, followed by KEGG pathway enrichment analysis and Pearson correlation analysis.
Results: Micro-CT showed that the bone volume fraction in the Tanshinone IIA group rebounded significantly compared with the model group, and the trabecular arrangement tended to be orderly. HE staining revealed alleviated adipocyte infiltration, and TRAP staining demonstrated a reduction in osteoclast number. Metabolomics revealed that xanthine, hypoxanthine, 2-oxopentanedioic acid, and succinic semialdehyde were markedly elevated in the model group, whereas these metabolites returned toward normal levels after Tanshinone IIA intervention. KEGG enrichment mainly involved purine metabolism, 2-oxocarboxylic acid metabolism, and amino acid metabolic pathways. Proteomics indicated that differentially expressed proteins in the model group were enriched in the Hippo, TGF-β, and Wnt signaling pathways, whereas Tanshinone IIA intervention primarily affected aminoacyl-tRNA biosynthesis and lipid metabolism pathways. Pearson correlation analysis identified Bmp6, Smoc2, Ihh, and Enpp2 as core candidate proteins.
Conclusion: These findings suggest that Tanshinone IIA may be associated with improved bone microarchitecture and reduced fatty infiltration in the SONFH rat model. The observed changes were associated with alterations in purine and energy metabolism, the Hippo/TGF-β/Wnt signaling pathways, and candidate proteins such as Bmp6 and Ihh. These results indicate potential multi-target associations at three levels—bone protection, metabolic alterations, and signaling network associations—providing preliminary correlative multi-omics evidence for further investigation in SONFH.
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BibTeX
@article{li2026insights,
title = {{Insights into potential multi-target protective effects of Tanshinone IIA in steroid-induced osteonecrosis of the femoral head: evidence from integrated metabolomics and proteomics}},
author = {Wei Li and Ning Xu and Jin-Lian Chai and Bo-Chun Zhang and Yan-Chen Liang and Gang Li and Xue-Zhen Liang},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1991120},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1991120/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Insights into potential multi-target protective effects of Tanshinone IIA in steroid-induced osteonecrosis of the femoral head: evidence from integrated metabolomics and proteomics
AU - Wei Li
AU - Ning Xu
AU - Jin-Lian Chai
AU - Bo-Chun Zhang
AU - Yan-Chen Liang
AU - Gang Li
AU - Xue-Zhen Liang
PY - 2026
DA - 2026/10/19
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1991120
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1991120/full
AB - Objective: To systematically evaluate the interventional effects of Tanshinone IIA on a rat model of steroid-induced osteonecrosis of the femoral head (SONFH) based on metabolomics and proteomics technologies, and to elucidate its multi-target regulatory mechanisms. Methods: Twenty-four SD rats were randomly divided into a Control group, a model group, and a Tanshinone IIA group, with eight rats in each group. Micro-CT, HE staining, and TRAP staining were used to assess the bone microarchitecture and pathological changes of the femoral head. UPLC-MS/MS-based untargeted metabolomics combined with DIA quantitative proteomics were employed to analyze the metabolite and protein expression profiles of fecal and femoral head samples. Differential metabolites and differentially expressed proteins were screened, followed by KEGG pathway enrichment analysis and Pearson correlation analysis. Results: Micro-CT showed that the bone volume fraction in the Tanshinone IIA group rebounded significantly compared with the model group, and the trabecular arrangement tended to be orderly. HE staining revealed alleviated adipocyte infiltration, and TRAP staining demonstrated a reduction in osteoclast number. Metabolomics revealed that xanthine, hypoxanthine, 2-oxopentanedioic acid, and succinic semialdehyde were markedly elevated in the model group, whereas these metabolites returned toward normal levels after Tanshinone IIA intervention. KEGG enrichment mainly involved purine metabolism, 2-oxocarboxylic acid metabolism, and amino acid metabolic pathways. Proteomics indicated that differentially expressed proteins in the model group were enriched in the Hippo, TGF-β, and Wnt signaling pathways, whereas Tanshinone IIA intervention primarily affected aminoacyl-tRNA biosynthesis and lipid metabolism pathways. Pearson correlation analysis identified Bmp6, Smoc2, Ihh, and Enpp2 as core candidate proteins. Conclusion: These findings suggest that Tanshinone IIA may be associated with improved bone microarchitecture and reduced fatty infiltration in the SONFH rat model. The observed changes were associated with alterations in purine and energy metabolism, the Hippo/TGF-β/Wnt signaling pathways, and candidate proteins such as Bmp6 and Ihh. These results indicate potential multi-target associations at three levels—bone protection, metabolic alterations, and signaling network associations—providing preliminary correlative multi-omics evidence for further investigation in SONFH.
SN - 1664-2392
ER -