Elucidation of the mechanism of human growth hormone-Fc fusion protein in accelerating tibial fracture healing in rats via untargeted metabolomics

Background Fracture 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. Methods By 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. Results The 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. Conclusion The 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.