Elucidation of the mechanism of human growth hormone-Fc fusion protein in accelerating tibial fracture healing in rats via untargeted metabolomics
Abstract
BackgroundFracture healing has always been a major challenge in clinical practice. This study aims to explore the effect of human growth hormone-Fc fusion protein on the healing of a rat tibial fracture model and its possible mechanisms of action.MethodsBy assessing the levels of growth hormone effectors IGF-1 and IGFBP-3 in rats, combined with Micro-CT scanning and pathological staining slices, we investigated the pathological effects of subcutaneous injection of human growth hormone-Fc fusion protein for 28 days on the healing of rat tibial fractures. Serum metabolomics studies were conducted using the AB Triple TOF 6600 mass spectrometer to further investigate the bio-metabolites relevant to fracture healing influenced by the human growth hormone-Fc fusion protein.ResultsThe study showed that after administration of the growth hormone-Fc fusion protein, IGF-1 and IGFBP-3 levels in rat blood were significantly increased. Micro-CT scans and pathological staining also demonstrated that the high-dose group had a marked promoting effect on fracture healing, with a healing rate significantly superior to the positive drug group; the medium and low dose groups also showed certain degrees of promotion. Metabolomic results revealed that the growth hormone could regulate 17 metabolites, affecting 8 metabolic pathways in relation to fracture healing.ConclusionThe study found that the growth hormone-Fc fusion protein shortened the healing period of the rat tibial fracture model by more than 1 week, possibly by influencing the levels of IGF-1 and IGFBP-3 factors, as well as regulating 17 metabolites in 8 metabolic pathways—including starch and sucrose metabolism, galactose metabolism, glycerophospholipid metabolism, terpene backbone biosynthesis, glyoxylate and dicarboxylate metabolism, retinol metabolism, glycine, serine, and threonine metabolism, and inositol phosphate metabolism—thus promoting fracture healing. This provides a basis for subsequent larger-scale, multicenter experiments and clinical translational research on FcGH in the treatment of fractures.
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BibTeX
@article{gu2026elucidation,
title = {{Elucidation of the mechanism of human growth hormone-Fc fusion protein in accelerating tibial fracture healing in rats via untargeted metabolomics}},
author = {Jianyang Gu and Juntong Liu and Binghuai Peng and Baisong Zhou and Zhuonan Li and Hao Zhang and Tianyu Zhang and Haoming Jiang and Ruixin Sun and Ping Gong and Han Liu},
journal = {Frontiers in Molecular Biosciences},
year = {2026},
month = oct,
doi = {10.3389/fmolb.2026.1971992},
url = {https://www.frontiersin.org/articles/10.3389/fmolb.2026.1971992},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Elucidation of the mechanism of human growth hormone-Fc fusion protein in accelerating tibial fracture healing in rats via untargeted metabolomics
AU - Jianyang Gu
AU - Juntong Liu
AU - Binghuai Peng
AU - Baisong Zhou
AU - Zhuonan Li
AU - Hao Zhang
AU - Tianyu Zhang
AU - Haoming Jiang
AU - Ruixin Sun
AU - Ping Gong
AU - Han Liu
PY - 2026
DA - 2026/10/28
JO - Frontiers in Molecular Biosciences
DO - 10.3389/fmolb.2026.1971992
UR - https://www.frontiersin.org/articles/10.3389/fmolb.2026.1971992
AB - BackgroundFracture healing has always been a major challenge in clinical practice. This study aims to explore the effect of human growth hormone-Fc fusion protein on the healing of a rat tibial fracture model and its possible mechanisms of action.MethodsBy assessing the levels of growth hormone effectors IGF-1 and IGFBP-3 in rats, combined with Micro-CT scanning and pathological staining slices, we investigated the pathological effects of subcutaneous injection of human growth hormone-Fc fusion protein for 28 days on the healing of rat tibial fractures. Serum metabolomics studies were conducted using the AB Triple TOF 6600 mass spectrometer to further investigate the bio-metabolites relevant to fracture healing influenced by the human growth hormone-Fc fusion protein.ResultsThe study showed that after administration of the growth hormone-Fc fusion protein, IGF-1 and IGFBP-3 levels in rat blood were significantly increased. Micro-CT scans and pathological staining also demonstrated that the high-dose group had a marked promoting effect on fracture healing, with a healing rate significantly superior to the positive drug group; the medium and low dose groups also showed certain degrees of promotion. Metabolomic results revealed that the growth hormone could regulate 17 metabolites, affecting 8 metabolic pathways in relation to fracture healing.ConclusionThe study found that the growth hormone-Fc fusion protein shortened the healing period of the rat tibial fracture model by more than 1 week, possibly by influencing the levels of IGF-1 and IGFBP-3 factors, as well as regulating 17 metabolites in 8 metabolic pathways—including starch and sucrose metabolism, galactose metabolism, glycerophospholipid metabolism, terpene backbone biosynthesis, glyoxylate and dicarboxylate metabolism, retinol metabolism, glycine, serine, and threonine metabolism, and inositol phosphate metabolism—thus promoting fracture healing. This provides a basis for subsequent larger-scale, multicenter experiments and clinical translational research on FcGH in the treatment of fractures.
SN - 2296-889X
ER -