Osteocalcin: A link between bone homeostasis and energy metabolism

García-Martín, Antonia; Reyes-García, Rebeca; Ávila-Rubio, Verónica; Muñóz-Torres, Manuel

doi:10.1016/j.endoen.2012.06.012

Cited by 6 publications

(7 citation statements)

References 21 publications

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“…Furthermore, REE is more closely associated with BMD (compared to BMI) in African American women [11]. Moreover, osteocalcin, leptin (a hormone that is derived from fat) and serotonin (an anorexigenic neurotransmitter in the brain) are closely related with bone remodeling and energy metabolism [6,[12][13][14]. When taken together, these findings suggest that basal metabolism in patients with T2D may be involved in bone metabolism.…”

Section: Introductionmentioning

confidence: 84%

Association between basal metabolic function and bone metabolism in postmenopausal women with type 2 diabetes

et al. 2015

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Section: Introductionmentioning

confidence: 84%

Association between basal metabolic function and bone metabolism in postmenopausal women with type 2 diabetes

et al. 2015

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“…In addition to its structural role, bone has come to be regarded as an endocrine organ that affects energy metabolism . Osteoporosis, occurring with aging especially in postmenopausal women, could then be considered a disorder of energy metabolism like obesity and diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to its structural role, bone has come to be regarded as an endocrine organ that affects energy metabolism. (3) Osteoporosis, occurring with aging especially in postmenopausal women, could then be considered a disorder of energy metabolism like obesity and diabetes. Here we found that knocking out Tgr5, a regulator of energy metabolism, enhanced osteoclast differentiation but had little effect on osteoblast differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…Osteoclasts are multinucleated giant cells derived from hematopoietic progenitor cells and are mitochondria‐rich cells with a high energy demand . Consequently, osteoporosis, like obesity and diabetes, could be another disorder of energy metabolism …”

Section: Introductionmentioning

confidence: 99%

“…(2) Consequently, osteoporosis, like obesity and diabetes, could be another disorder of energy metabolism. (3)(4)(5) AMP-activated protein kinase (AMPK) has emerged over the last decade as a key sensing mechanism in the regulation of cellular energy homeostasis. In particular, AMPK signaling is associated with a decline in the capacity to respond to metabolic alterations during aging and is directly involved in several ageassociated diseases, including metabolic syndrome, (6) cardiovascular disorders, (7) neurodegenerative disorders, (8) osteoarthritis, and amyotrophic lateral sclerosis.…”

Section: Introductionmentioning

confidence: 99%

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Dual Targeting of Bile Acid Receptor-1 (TGR5) and Farnesoid X Receptor (FXR) Prevents Estrogen-Dependent Bone Loss in Mice

Huang

Wang

et al. 2018

Journal of Bone and Mineral Research

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Osteoporosis is a global bone disease characterized by reduced bone mineral density (BMD) and increased risk of fractures. The risk of developing osteoporosis increases with aging, especially after menopause in women. Discovering the signaling pathways that play a significant role in aging‐ and menopause‐induced osteoporosis should accelerate osteoporosis drug discovery. In this study, we found that bile acid membrane receptor Tgr5 knockout C57BL/6J mice had similar bone mass as wild‐type mice during early and middle‐age (before 4 months old) bone remodeling; however, Tgr5‐/‐ markedly decreased bone mass in aged (more than 7 months old) and ovariectomized (OVX) mice compared with wild‐type mice. Moreover, Tgr5 knockout strongly induced osteoclast differentiation but had no effect on osteoblast activity. Treatment with different TGR5 agonists consistently inhibited osteoclast differentiation. Importantly, our results showed that Tgr5 regulates osteoclastogenesis by the AMP‐activated protein kinase (AMPK) signaling pathway, which is a central metabolic pathway involved in the pathophysiology of aging and age‐related diseases. The bile acid nuclear receptor FXR is an established regulator of bone metabolism. We screened the derivatives of betulinic acid (BA), a known TGR5 agonist, to identify novel dual agonists of FXR and TGR5. The derivative SH‐479, a pentacyclic triterpene acid, could activate both TGR5 and FXR, with a better inhibitory effect on osteoclastogenesis compared with agonists solely activating FXR or TGR5 and additionally enhanced osteoblastogenesis. Furthermore, SH‐479 therapeutically abrogated bone loss in C57BL/6J mice through the bone remodeling pathways. Together, our results demonstrate that dual targeting the bile acid membrane receptor TGR5 and nuclear receptor FXR is a promising strategy for osteoporosis. © 2018 American Society for Bone and Mineral Research.

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Integration of metabolomics and transcriptomics provides insights into enhanced osteogenesis in Ano5Cys360Tyr knock-in mouse model

Liu

Miao

et al. 2023

Front. Endocrinol.

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IntroductionGnathodiaphyseal dysplasia (GDD; OMIM#166260) is a rare autosomal dominant disorder characterized by diaphyseal sclerosis of tubular bones and cemento-osseous lesions in mandibles. GDD is caused by point mutations in the ANO5 gene. However, the mechanisms underlying GDD have not been disclosed. We previously generated the first knock-in mouse model for GDD expressing a human mutation (p.Cys360Tyr) in ANO5 and homozygous Ano5 knock-in (Ano5KI/KI) mice exhibited representative traits of human GDD especially including enhanced osteogenesis.MethodsMetabolomics and transcriptomics analyses were conducted for wildtype (Ano5+/+) and Ano5KI/KI mature mouse calvarial osteoblasts (mCOBs) grown in osteogenic cultures for 14 days to identify differential intracellular metabolites and genes involved in GDD. Subsequently, related differential genes were validated by qRT-PCR. Cell proliferation was confirmed by CCK8 assay and calcium content in mineral nodules was detected using SEM-EDS.ResultsMetabolomics identified 42 differential metabolites that are primarily involved in amino acid and pyrimidine metabolism, and endocrine and other factor-regulated calcium reabsorption. Concomitantly, transcriptomic analysis revealed 407 differentially expressed genes in Ano5KI/KI osteoblasts compared with wildtype. Gene ontology and pathway analysis indicated that Ano5Cys360Tyr mutation considerably promoted cell cycle progression and perturbed calcium signaling pathway, which were confirmed by validated experiments. qRT-PCR and CCK-8 assays manifested that proliferation of Ano5KI/KI mCOBs was enhanced and the expression of cell cycle regulating genes (Mki67, Ccnb1, and Ccna2) was increased. In addition, SEM-EDS demonstrated that Ano5KI/KI mCOBs developed higher calcium contents in mineral nodules than Ano5+/+ mCOBs, while some calcium-related genes (Cacna1, Slc8a1, and Cyp27b1) were significantly up-regulated. Furthermore, osteocalcin which has been proved to be an osteoblast-derived metabolic hormone was upregulated in Ano5KI/KI osteoblast cultures.DiscussionOur data demonstrated that the Ano5Cys360Tyr mutation could affect the metabolism of osteoblasts, leading to unwonted calcium homeostasis and cellular proliferation that can contribute to the underlying pathogenesis of GDD disorders.

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Osteocalcin: A link between bone homeostasis and energy metabolism

Cited by 6 publications

References 21 publications

Association between basal metabolic function and bone metabolism in postmenopausal women with type 2 diabetes

Association between basal metabolic function and bone metabolism in postmenopausal women with type 2 diabetes

Dual Targeting of Bile Acid Receptor-1 (TGR5) and Farnesoid X Receptor (FXR) Prevents Estrogen-Dependent Bone Loss in Mice

Integration of metabolomics and transcriptomics provides insights into enhanced osteogenesis in Ano5Cys360Tyr knock-in mouse model

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