Metabolomic Associations with Serum Bone Turnover Markers

Bellissimo, Moriah P.; Roberts, Joseph L.; Jones, Dean P.; Liu, Ken H.; Taibl, Kaitlin R.; Uppal, Karan; Weitzmann, M. Neale; Pacifici, Roberto; Drissi, Hicham; Ziegler, Thomas R.; Alvarez, Jessica A.

doi:10.3390/nu12103161

Cited by 22 publications

(22 citation statements)

References 70 publications

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“…We observed that females had greater biomarkers of bone resorption (CTX1 and CTX/P1NP) than males. In a study investigating healthy young adult serum using metabolomics and biomarker analysis CTX1 was positively correlated with lipid metabolism (fatty acid biosynthesis), beta oxidation, and carbohydrate metabolism in humans (66) . Previous studies found that osteoclasts' high energy demand can be fueled by lipids (66,(79)(80)(81) , but it is uncertain if osteoblasts and osteocytes are fueled by lipids in the same way.…”

Section: Discussionmentioning

confidence: 99%

“…Other mechanisms of tryptophan prominently affecting bone remodeling is through stimulating proliferation and differentiation of osteoblasts and bone marrow mesenchymal stem cells (87) . In both humans and mice, tryptophan has been associated with osteoclast activity and was positively associated with CTX1 levels (66) . In our study, there was a moderate correlation between bone strength and CTX1/P1NP for males.…”

Section: Discussionmentioning

confidence: 99%

“…Males had elevated P1NP, lower CTX1, and upregulated amino acid metabolism. Metabolic pathways previously associated with P1NP include energy metabolism (e.g., TCA cycle), amino acid metabolism, and pyrimidine metabolism (66) . Energy and amino acid metabolism were also upregulated in male isolated cortical bone.…”

Section: Discussionmentioning

confidence: 99%

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The cortical bone metabolome of C57BL/6J mice is sexually dimorphic

Welhaven

Vahidi

Walk

et al. 2021

Preprint

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The material properties of bone tissue depend on the activity of remodeling bone cells, but the impact of bone cell metabolism on bone tissue is uncertain. To date, the metabolome of bone has not been evaluated for cortical bone, bone marrow, or whole bone including both tissue types. Furthermore, it is of particular interest whether the cortical bone metabolome reflects the sexual dimorphism observed in cortical bone material properties. We hypothesized that the metabolome of cortical bone differs from that of bone marrow, and that the cortical bone metabolome is sexually dimorphic. We first evaluated the metabolic profiles of isolated cortical bone, bone marrow, and whole bone for 20-week female C57Bl/6 mice (n = 10). We then compared metabolic profiles for isolated cortical bone from a separate group of 20-week female and male C57Bl6/mice (n = 10 / sex). Femurs from the same mice were evaluated for flexural material properties. Strength groupings (high strength males, high strength females, low strength males) were utilized to inform comparisons in the isolated humerus cortical bone metabolome. The metabolome of isolated cortical bone, bone marrow, and whole bone are distinct. The isolated cortical bone metabolome is also distinct between males and females. The female mice show evidence of lipid metabolism, whereas male mice show evidence of amino acid metabolism. Finally, 12 metabolic pathways were differentially regulated between bones that differed in strength. High-strength bones from both male and female mice included metabolites associated with tryptophan and purine metabolism. Taken together, these data demonstrate the power of metabolomics to provide insight into the effects of metabolism on bone physiology. These data add to an intricate picture of bone as an organ that is sexually dimorphic both in material and metabolomic profiles.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The cortical bone metabolome of C57BL/6J mice is sexually dimorphic

Welhaven

Vahidi

Walk

et al. 2021

Preprint

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“…A plasma metabolomics study involving 34 adult women found that the serum C-terminal telopeptide (CTX) concentration, an index of bone resorption, was related to lipid and fatty acid metabolism pathways, but not carbohydrate metabolism. Osteoclasts in the active bone resorption state show a high capacity for fatty acid β oxidation, suggesting that the high energy state of active osteoclasts may be mainly supported by lipid catabolism ( 127 ). Short-chain fatty acids (SCFAs) inhibit osteoclast production in vivo and in vitro ( 128 ).…”

Section: Other Substrates For Energy Metabolismmentioning

confidence: 99%

The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

Lin

Zhu

2021

Front. Endocrinol.

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In recent decades, the mechanism underlying bone metabolic disorders based on energy metabolism has been heavily researched. Bone resorption by osteoclasts plays an important role in the occurrence and development of osteoporosis. However, the mechanism underlying the osteoclast energy metabolism disorder that interferes with bone homeostasis has not been determined. Bone resorption by osteoclasts is a process that consumes large amounts of adenosine triphosphate (ATP) produced by glycolysis and oxidative phosphorylation. In addition to glucose, fatty acids and amino acids can also be used as substrates to produce energy through oxidative phosphorylation. In this review, we summarize and analyze the energy-based phenotypic changes, epigenetic regulation, and coupling with systemic energy metabolism of osteoclasts during the development and progression of osteoporosis. At the same time, we propose a hypothesis, the compensatory recovery mechanism (involving the balance between osteoclast survival and functional activation), which may provide a new approach for the treatment of osteoporosis.

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“…The crosslinking process of bone collagen is essential for bone substation formation and is considered important in bone reconstruction [ 90 ] and fracture healing. Bone conversion markers, type I pre-collagen N-end peptides and type I collagen C-end peptides, such as provide sensitive indicators of bone formation and bone absorption, respectively [ 92 ]. Metabolomics-based studies have reported correlations found with amino acid and bone health assessments [ 93 – 95 ].…”

Section: Energy Metabolism (Glucose Amino Acid and Fat) In Bonementioning

confidence: 99%

Circadian rhythms affect bone reconstruction by regulating bone energy metabolism

et al. 2021

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Metabolism is one of the most complex cellular biochemical reactions, providing energy and substances for basic activities such as cell growth and proliferation. Early studies have shown that glucose is an important nutrient in osteoblasts. In addition, amino acid metabolism and fat metabolism also play important roles in bone reconstruction. Mammalian circadian clocks regulate the circadian cycles of various physiological functions. In vertebrates, circadian rhythms are mediated by a set of central clock genes: muscle and brain ARNT like-1 (Bmal1), muscle and brain ARNT like-2 (Bmal2), circadian rhythmic motion output cycle stagnates (Clock), cryptochrome 1 (Cry1), cryptochrome2 (Cry2), period 1 (Per1), period 2 (Per2), period 3 (Per3) and neuronal PAS domain protein 2 (Npas2). Negative feedback loops, controlled at both the transcriptional and posttranslational levels, adjust these clock genes in a diurnal manner. According to the results of studies on circadian transcriptomic studies in several tissues, most rhythmic genes are expressed in a tissue-specific manner and are affected by tissue-specific circadian rhythms. The circadian rhythm regulates several activities, including energy metabolism, feeding time, sleeping, and endocrine and immune functions. It has been reported that the circadian rhythms of mammals are closely related to bone metabolism. In this review, we discuss the regulation of the circadian rhythm/circadian clock gene in osteoblasts/osteoclasts and the energy metabolism of bone, and the relationship between circadian rhythm, bone remodeling, and energy metabolism. We also discuss the therapeutic potential of regulating circadian rhythms or changing energy metabolism on bone development/bone regeneration.

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Metabolomic Associations with Serum Bone Turnover Markers

Cited by 22 publications

References 70 publications

The cortical bone metabolome of C57BL/6J mice is sexually dimorphic

The cortical bone metabolome of C57BL/6J mice is sexually dimorphic

The Role of Osteoclast Energy Metabolism in the Occurrence and Development of Osteoporosis

Circadian rhythms affect bone reconstruction by regulating bone energy metabolism

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