Metabolomics-driven exploration of relationships among kidney, bone marrow and bone of rats with postmenopausal osteoporosis

Introduction Postmenopausal osteoporosis (PMOP) poses a great threat to women's health. Although the kidney, bone marrow and bone play crucial roles in PMOP, there are no multi-tissue metabolomics studies on the possible relationships among the three tissues.

Objectives The purpose of this research was to determine the metabolic changes of kidney, bone marrow and bone in the ovariectomized (OVX) rats, analyze their physiological functions, and investigate the relationships among the three tissues from the perspective of metabolomics.

Methods Gas chromatography-mass spectrometry (GC-MS) was used to analyze the metabolic profiling. Multivariate statistical analysis and pathway analysis were used to explore the metabolic changes and relationships of the three tissues in the OVX rats.

Results The number of differential metabolites in kidney, bone marrow and bone between the normal and OVX rats were 37, 16 and 17, respectively, which involved multiple metabolic pathways. The common differential metabolites of the three tissues were N-methyl-L-alanine. Kidney and bone marrow had common differential metabolites, including N-methyl-L-alanine, 2-hydroxybutyric acid, (R)-3-hydroxybutyric acid (β-hydroxybutyric acid, βHBA), urea and dodecanoic acid. There were three common differential metabolites of kidney and bone, including N-methyl-L-alanine, α-tocopherol and isofucostanol. The common differential metabolite of bone marrow and bone was N-methyl-L-alanine. The common metabolic pathways involved in the differential metabolites of the three tissues were fatty acid biosynthesis and aminoacyl-tRNA biosynthesis. The metabolic network of the OVX rats were constructed to show the metabolic relationships among the three tissues.

Conclusion Our study showed that profound metabolic changes have taken place in the kidney, bone marrow and bone, involving common differential metabolites and metabolic pathways. The evaluation of the metabolite function strengthened the understanding of the kidney-bone axis and the metabolic relationships among the three tissues of OVX rats.