Osteocalcin promotes proliferation, differentiation, and survival of PC12 cells

Ando, Eika; Higashi, Sen; Mizokami, Akinari; Watanabe, Seiji; Hirata, Masato; Takeuchi, Hiroshi

doi:10.1016/j.bbrc.2021.03.146

Cited by 7 publications

(8 citation statements)

References 32 publications

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“…59 In addition, cellular experiments showed that osteocalcin promoted neuronal cell survival and suppressed H 2 O 2 -induced cell death. 60 In the study we also demonstrated that the changes of VCD mice induced by exercise were significantly related to osteocalcin level. Given the role of osteocalcin in regulating anxiety and neuronal apoptosis and considering of our results, we postulated that exercise ameliorated anxiety in VCD mice by promoting hippocampal neurogenesis and inhibiting hippocampal neuronal apoptosis, at least in part, are mediated by increasing circulating osteocalcin.…”

Section: Discussionsupporting

confidence: 54%

Exercise ameliorates anxious behavior and promotes neuroprotection through osteocalcin in VCD‐induced menopausal mice

et al. 2023

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AimsAs the ovaries age and women transition to menopause and postmenopause, reduced estradiol levels are associated with anxiety and depression. Exercise contributes to alleviate anxiety and depression and the bone‐derived hormone osteocalcin has been reported to be necessary to prevent anxiety‐like behaviors. The aim of this study was to investigate the effects of exercise on anxiety behaviors in climacteric mice and whether it was related to osteocalcin.MethodsMenopausal mouse model was induced by intraperitoneal injection of 4‐vinylcyclohexene diepoxide (VCD). Open field, elevated plus maze, and light–dark tests were used to detect anxious behavior in mice. The content of serum osteocalcin was measured and its correlation with anxiety behavior was analyzed. BRDU and NEUN co‐localization cells were detected with immunofluorescence. Western blot was applied to obtain apoptosis‐related proteins.ResultsThe VCD mice showed obvious anxiety‐like behaviors and 10 weeks of treadmill exercise significantly ameliorated the anxiety and increased circulating osteocalcin in VCD mice. Exercise increased the number of BRDU and NEUN co‐localization cells in hippocampal dentate gyrus, reduced the number of impaired hippocampal neurons, inhibited the expression of BAX, cleaved Caspase3, and cleaved PARP, promoted the expression of BCL‐2. Importantly, circulating osteocalcin levels were positively associated with the improvements of anxiety, the number of BRDU and NEUN co‐localization cells in hippocampal dentate gyrus and negatively related to impaired hippocampal neurons.ConclusionExercise ameliorates anxiety behavior, promotes hippocampal dentate gyrus neurogenesis, and inhibits hippocampal cell apoptosis in VCD‐induced menopausal mice. They are related to circulating osteocalcin, which are increased by exercise.

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Section: Discussionsupporting

confidence: 54%

Exercise ameliorates anxious behavior and promotes neuroprotection through osteocalcin in VCD‐induced menopausal mice

et al. 2023

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“…Yet, probably the most critical consequence of the identification of Gprc6a as a receptor of osteocalcin has been to allow the study of the biology of osteocalcin in humans as will be described below. More broadly, it gave to osteocalcin a more complete hormonal identity, which has now been confirmed by numerous independent cell culture studies, in vivo studies in multiple species and multiple disease models, by correlative studies in humans and as we will describe, human genetic evidence [37,42,45–120]. It was also confirmed even more recently by the generation of a new genetic model of Osteocalcin deficiency [50].…”

Section: The Foreseen Functions Of Osteocalcinmentioning

confidence: 78%

“…It was also confirmed even more recently by the generation of a new genetic model of Osteocalcin deficiency [50]. While the evidence indicating that osteocalcin acts as a hormone in rodents and primates grows at an increasing pace, as the sample of references presented above indicates [37,42,45–120], this does not mean that there are no studies in which Osteocalcin ‐deficient mice were presented as normal [51].…”

Section: The Foreseen Functions Of Osteocalcinmentioning

confidence: 99%

Osteocalcin and the physiology of danger

Berger

Karsenty

2022

FEBS Letters

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Bone biology has long been driven by the question as to what molecules affect cell differentiation or the functions of bone. Exploring this issue has been an extraordinarily powerful way to improve our knowledge of bone development and physiology. More recently, a second question has emerged: does bone have other functions besides making bone? Addressing this conundrum revealed that the bone‐derived hormone osteocalcin affects a surprisingly large number of organs and physiological processes, including acute stress response. This review will focus on this emerging aspect of bone biology taking osteocalcin as a case study and will show how classical and endocrine functions of bone help to define a new functional identity for this tissue.

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“…In another study, it was determined that serum adiponectin administration to rats fed a high-fat diet for four weeks and developing IR and dyslipidemia provided both PPARγ activation and a decrease in IR and dyslipidemia [80]. Also, it was reported that GluOC administered intraperitoneally or even orally can improve high-fat-diet-induced diabetic status [81]. In a study on pregnant individuals, it was found that serum adiponectin levels showed an inverse correlation with HOMA-IR at 32 weeks of pregnancy [82].…”

Section: The Potential Role Of Osteocalcin In the Treatment Of Obesitymentioning

confidence: 99%

Osteocalcin: A new phenomenon for type 2 diabetes and obesity

Koçak

Tek

2023

EUR J ENV PUBLIC HLT

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Objectives: The molecular biology revolution has emerged with the determination that bone tissue is an endocrine organ that regulates many physiological processes, and osteocalcin (OCN), an osteoblast-derived protein that provides endocrine control, is a hormone that regulates glucose and energy homeostasis. By controlling gene expression in β-cells and adipocytes, OCN improves glucose intolerance, obesity, and insulin expression. In addition, OCN stimulates the secretion of adiponectin, a molecule that increases fatty acid oxidation and insulin secretion and sensitivity in adipose tissue and reduces adipose tissue accumulation. Recent research suggests that serum OCN increases the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and uncoupling protein-1 (UCP1) genes, which play a role in thermogenesis in brown adipose tissue, it also affects insulin sensitivity by increasing adiponectin expression in white adipose tissue. OCN the target gene of insulin, and resting energy expenditure and mitochondrial biogenesis. With all these effects, OCN is a protein that has recently been found to be associated with diabetes and obesity components. Conclusions: This review aims to present an overview of understanding the interaction of OCN produced by osteoblasts with insulin, glucose metabolism, adipose tissue, skeletal and muscle tissue, and appetite metabolism in understanding the endocrine functions of bone. In addition, it was conducted to examine the role of OCN in energy metabolism and to evaluate the relationship of energy metabolism pathways affected by OCN with non-communicable chronic diseases such as type 2 diabetes mellitus and obesity.

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Osteocalcin promotes proliferation, differentiation, and survival of PC12 cells

Cited by 7 publications

References 32 publications

Exercise ameliorates anxious behavior and promotes neuroprotection through osteocalcin in VCD‐induced menopausal mice

Exercise ameliorates anxious behavior and promotes neuroprotection through osteocalcin in VCD‐induced menopausal mice

Osteocalcin and the physiology of danger

Osteocalcin: A new phenomenon for type 2 diabetes and obesity

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