It turns out that the interpretation of the findings is that the upregulated substances have a protective effect.Very nice, thanks for posting it! It deserves an in-depth reading, which I plan to do later today.
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GC-MS based comparative metabolomic analysis of human cancellous bone reveals the critical role of linoleic acid metabolism in femur head necrosis - MetabolomicsIntroduction Femur head necrosis (FHN) is a challenging clinical disease with unclear underlying mechanism, which pathologically is associated with disordered metabolism. However, the disordered metabolism in cancellous bone of FHN was never analyzed by gas chromatography-mass spectrometry...link.springer.com
GC-MS based comparative metabolomic analysis of human cancellous bone reveals the critical role of linoleic acid metabolism in femur head necrosis
Femur head necrosis (FHN) is a challenging clinical disease with unclear underlying mechanism, which pathologically is associated with disordered metabolism. However, the disordered metabolism in cancellous bone of FHN was never analyzed by gas chromatography-mass spectrometry (GC-MS).
To elucidate altered metabolism pathways in FHN and identify putative biomarkers for the detection of FHN.
We recruited 26 patients with femur head necrosis and 22 patients with femur neck fracture in this study. Cancellous bone tissues from the femoral heads were collected after the surgery and were analyzed by GC-MS based untargeted metabolomics approach. The resulting data were analyzed via uni- and multivariate statistical approaches. The changed metabolites were used for the pathway analysis and potential biomarker identification.
Thirty-seven metabolites distinctly changed in FHN group were identified. Among them, 32 metabolites were upregulated and 5 were downregulated in FHN. The pathway analysis showed that linoleic acid metabolism were the most relevant to FHN pathology. On the basis of metabolites network, L-lysine, L-glutamine and L-serine were deemed as the junctions of the whole metabolites. Finally, 9,12-octadecadienoic acid, inosine, L-proline and octadecanoic acid were considered as the potential biomarkers of FHN.
This study provides a new insight into the pathogenesis of FHN and confirms linoleic acid metabolism as the core.
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Linoleic acid is considered the main source of stearic acid beneficial for osteogenesis.
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Based on the pathway analysis and the enrichment anlalysis, we confirmed the importance of linoleic acid metabolism in FHN bone. Linoleic acid is a doubly unsaturated fatty acid, also known as an omega-6 fatty acid, existing widely in plant glycosides. Its metabolism was related to a lot of important biological processes, including osteogenic differentiation, adipogenesis and stem cell aging. According to the study of Yuan S, higher plasma linoleic acid and oleic acid levels was positively associated with bone mineral density and inversely associated with the odds of fracture (Yuan et al., 2019). Platt ID et al.. reported that different linoleic acid might had variable function on bone formation and adiposity in vivo and in vitro (Platt & El-Sohemy, 2009). Besides the osteogenesis, linoleic acid regulate the procedure of adipogenesis. As in the study of Turner PA et al., linoleic acid supplementation was reported to result in enhanced adipogenesis (Turner et al., 2018). The team of Yu C also reported
that linoleic acid significantly promoted lipid accumulation, probably by regulating PPARγ phosphorylation in adipocytes (Yu et al., 2017). In addition, linoleic acid metabolism was one of the most significant pathways involved in the response to the reperfusion after cerebral ischemia (Chen et al., 2023). In this study, linoleic acid metabolism with high impact value was the most relevant pathway with FHN. The change in linoleic acid metabolism might regulate the osteogenesis and adipogenesis in FHN.
It seemed that the candidate biomarkers were some protective metabolites against the bone necrosis. On the basis of metabolite-metabolite network analysis, 3 amino acids, including L-lysine, L-glutamine and L-serine located at the vital junctions of the whole altered metabolites. L- Lysine is an important metabolite which can regulate the bone turnout. Poly-L-lysine, with its highly biocompatible molecules, is commonly used as pseudobiomaterials to induce osteogenesis (Izumiya et al., 2021) and to facilitate bone defect regeneration (Tao et al., 2022). L-Glutamine is nonessential amino acid that can become conditionally essential under stress conditions (Dos Santos et al., 2017). It is used to support osteoblast differentiation and bone development (Sharma et al., 2021). A constant supply of glutamine was required for bone-forming osteoblast and bone-resorbing osteoclast cells (Srivastava et al., 2022). L-serine is a multifunctional molecule in many metabolic processes, such as cysteine biosynthetic process from serine, transferase activity and catalyzation of the attachment of serine to tRNA (Overington et al., 2006; Sen & Banerjee, 2007; Yard et al., 2007). O-Phospho-L-serine amino acids have a favorable influence by enhancing the in vitro viability of osteoblasts in these modified materials (Salgado et al., 2019). The changed amino acids in our metabolite network might regulate the osteoclasis-osteogenesis balance in FHN. In this study, some fatty acids, such as arachidonic acid,
octadecanoic acid, trans-9-octadecenoic acid, decanoic acid, heptadecanoic acid and decanedioic acid increased in FHN. Arachidonic acid reduces bone mineral content without impacting bone strength in growing male rats (Mak et al., 2019). It can protect the bone formation by inhibiting osteoclast formation (Kasonga et al., 2019). Octadecanoic acid and hexadecanoic acid could promote osteoblast cell attachment and proliferation (Venugopal et al., 2018). Decanoic acid at particular concentration stimulated the proliferation of human osteoblast (MG63) cells (Venugopal et al., 2017).
Our future work is to verify the key enzymes in linoleic acid metabolism and some amino acids metabolism in FHN on the protein and gene level in FHN.
Our findings elucidates the pathophysiology of femur head necrosis. Disturbances of linoleic acid metabolism might be associated with the FHN pathologies. L-lysine, L-glutamine and L-serine located in the cores of all the changed metabolites. In addition, 9,12-octadecadienoic acid, inosine, L-proline and octadecanoic acid may serve as potential biomarkers for FHN.