NDLI: The association between metabolite profiles and impaired bone microstructure in adult growth hormone deficient rats

Content Provider	Springer Nature : BioMed Central
Author	Guo, Xiaonan Liu, Shanshan Hu, Wenjing Lyu, Xiaorui Xu, Hanyuan Zhu, Huijuan Pan, Hui Wang, Linjie Wan, Yu Yang, Hongbo Gong, Fengying
Abstract	Background Adult growth hormone deficiency (AGHD) is associated with an increased risk of fractures and impaired bone microstructure. Understanding the metabolic changes accompanying bone deterioration in AGHD might provide insights into mechanisms behind molecular changes and develop new biomarkers or nutritional strategies for bone destruction. Our study aimed to investigate the association between altered metabolite patterns and impaired bone microstructure in adult rats with growth hormone deficiency. Methods Thirty seven-week-aged adult Lewis dwarf homozygous (dw/dw) rats (five females and five males), and adult Lewis dwarf heterozygous (dw/ +) rats (five females and five males) rats were compared. Micro-computed tomography (Micro-CT) was used to examine the bone's microstructure. Hematoxylin and eosin (H&E) staining were used to quantify the histological characteristics. Liquid chromatography-mass spectrometry untargeted serum metabolomic analysis was applied in the study. ELISA was used to measure serum bone turnover markers and IGF-1 levels. Results Adult dw/dw rats exhibited great reductions in trabecular volume bone density (Tb.vBMD), bone volume/total volume (BV/TV), and cortical thickness (Ct. Th) compared with adult dw/ + rats (all p values < 0.05), indicating significant impairment in bone microstructure. The serum metabolite profiles revealed substantial differences between the dw/dw rats and dw/ + rats. A total of 134 differential metabolites in positive ion mode and 49 differential metabolites in negative mode were identified. Five metabolites, including Lysophosphatidylcholine(LPC) 20:3, LPC22:6, LPC22:4, cortisol and histamine levels were upregulated in dw/dw rats. The steroid hormone biosynthesis and bile secretion pathways were the main perturbed metabolic pathways. There were significant associations between differential metabolites and the impaired bone microstructure parameters, indicating that the selected metabolites might serve as potential biomarkers for deteriorated bone microstructure in AGHD. Conclusion Adult dw/dw rats exhibit impaired bone microstructure and distinct serum metabolic profiles, and the altered metabolites were significantly associated with bone microstructure destruction. This provides a new insight into understanding the mechanism of bone deterioration in AGHD patients from a metabolic perspective.
Related Links	https://bmcmusculoskeletdisord.biomedcentral.com/counter/pdf/10.1186/s12891-024-08010-y.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	14712474
DOI	10.1186/s12891-024-08010-y
Journal	BMC Musculoskeletal Disorders
Issue Number	1
Volume Number	25
Language	English
Publisher	BioMed Central
Publisher Date	2024-11-06
Access Restriction	Open
Subject Keyword	Orthopedics Rehabilitation Rheumatology Sports Medicine Internal Medicine Epidemiology Adult growth hormone deficiency Insulin-like growth hormone 1 Bone microstructure Micro-CT Serum metabolomics
Content Type	Text
Resource Type	Article
Subject	Orthopedics and Sports Medicine Rheumatology
Journal Impact Factor	2.2/2023
5-Year Journal Impact Factor	2.6/2023

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