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

IF 2.2 3区 医学 Q2 ORTHOPEDICS
Xiaonan Guo, Shanshan Liu, Wenjing Hu, Xiaorui Lyu, Hanyuan Xu, Huijuan Zhu, Hui Pan, Linjie Wang, Yu Wan, Hongbo Yang, Fengying Gong
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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.

缺乏生长激素的成年大鼠体内代谢物特征与骨骼微观结构受损之间的关联。
背景:成人生长激素缺乏症(AGHD)与骨折风险增加和骨微结构受损有关。了解伴随 AGHD 骨质恶化的代谢变化可能有助于深入了解分子变化背后的机制,并开发新的生物标志物或针对骨质破坏的营养策略。我们的研究旨在调查生长激素缺乏症成年大鼠代谢物模式改变与骨微结构受损之间的关联:方法:将 30 只 7 周龄的成年 Lewis 侏儒同基因(dw/dw)大鼠(5 只雌性和 5 只雄性)与成年 Lewis 侏儒异基因(dw/ +)大鼠(5 只雌性和 5 只雄性)进行比较。显微计算机断层扫描(Micro-CT)用于检查骨骼的微观结构。血红素和伊红(H&E)染色用于量化组织学特征。研究还采用了液相色谱-质谱非靶向血清代谢组分析法。采用 ELISA 法检测血清骨转换标志物和 IGF-1 水平:结果:与成年 dw/ + 大鼠相比,成年 dw/dw 大鼠的骨小梁体积骨密度(Tb.vBMD)、骨体积/总体积(BV/TV)和皮质厚度(Ct:成年 dw/dw 大鼠表现出受损的骨微观结构和独特的血清代谢特征,代谢物的改变与骨微观结构的破坏显著相关。这为从代谢角度了解 AGHD 患者骨质退化的机制提供了新的视角。
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来源期刊
BMC Musculoskeletal Disorders
BMC Musculoskeletal Disorders 医学-风湿病学
CiteScore
3.80
自引率
8.70%
发文量
1017
审稿时长
3-6 weeks
期刊介绍: BMC Musculoskeletal Disorders is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of musculoskeletal disorders, as well as related molecular genetics, pathophysiology, and epidemiology. The scope of the Journal covers research into rheumatic diseases where the primary focus relates specifically to a component(s) of the musculoskeletal system.
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