Circadian Rhythms in Serum Bone Markers and Their Relation to the Effect of Etidronate in Rats

Shao, Ping; Ohtsuka-Isoya, Mie; Satoh, Hisashi

doi:10.1081/cbi-120019343

Cited by 43 publications

(30 citation statements)

References 30 publications

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“…A significant body of literature examining serum protein biomarkers supports a role for circadian mechanisms in bone metabolism in both experimental models and clinical investigations in humans [120,[126][127][128][129][130][131][132][133][134][135][136]. These findings all have potential clinical implications relating to bone metabolism and patient care.…”

Section: The Circadian Clock and Clinical Treatmentsmentioning

confidence: 87%

A fluorescence spotlight on the clockwork development and metabolism of bone

et al. 2011

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Biological phenomena that exhibit periodic activity are often referred as biorhythms or biological clocks. Among these, circadian rhythms, cyclic patterns reflecting a 24-h cycle, are the most obvious in many physiological activities including bone growth and metabolism. In the late 1990s, several clock genes were isolated and their primary structures and functions were identified. The feedback loop model of transcriptional factors was proposed to work as a circadian core oscillator not only in the suprachiasmatic nuclei of the anterior hypothalamus, which is recognized as the mammalian central clock, but also in various peripheral tissues including cartilage and bone. Looking back to embryonic development, the fundamental architecture of skeletal patterning is regulated by ultradian clocks that are defined as biorhythms that cycle more than once every 24 h. As post-genomic approaches, transcriptome analysis by micro-array and bioimaging assays to detect luminescent and fluorescent signals have been exploited to uncover a more comprehensive set of genes and spatio-temporal regulation of the clockwork machinery in animal models. In this review paper, we provide an overview of topics related to these molecular clocks in skeletal biology and medicine, and discuss how fluorescence imaging approaches can contribute to widening our views of this realm of biomedical science.

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Section: The Circadian Clock and Clinical Treatmentsmentioning

confidence: 87%

A fluorescence spotlight on the clockwork development and metabolism of bone

et al. 2011

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“…If so, there must be some aging intrinsic changes or signalling pathway with respect to their differentiation potential. Aging alters the circadian biology in several aspects including the circadian components [29] and there have been clues linking circadian rhythms to bone metabolism: clinical studies have detected 24-h oscillations in human serum levels of osteocalcin and alkaline phosphatase [30, 31]. A recent study showed that a circadian gene could mediate leptin-dependent bone formation [32].…”

Section: Discussionmentioning

confidence: 99%

Age-related BMAL1 change affects mouse bone marrow stromal cell proliferation and osteo-differentiation potential

Chen¹,

Xu²,

Tan³

et al. 2012

aoms

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IntroductionAging people's bone regeneration potential is always impaired. Bone marrow stromal cells (MSCs) contain progenitors of osteoblasts. Donor age may affect MSCs’ proliferation and differentiation potential, but the genomic base is still unknown. Due to recent research's indication that a core circadian component, brain and muscle ARNT-like 1 protein (BMAL1), has a role in premature aging, we investigated the normal aging mechanism in mice with their MSCs and Bmal1 gene/protein level.Material and methods1, 6 and 16 month old C57BL/6 mice were used and the bone marrow stromal cells were gained and cultured at early passage. Bmal1 gene and protein level were detected in these cells. Marrow stromal cells were also induced to differentiate to osteoblasts or adipocytes. Three groups of mice MSCs were compared on proliferation by flow cytometry, on cell senescence by SA-β-gal expression and after osteo-induction on osteogenic potential by the expression of osterix (Osx), alkaline phosphatase (ALP) and osteocalcin (OCN).ResultsBmal1 gene and protein level as well as S-phase fraction of the cell cycle decreased in MSCs along with the aging process. At the same time, SA-β-gal+ levels increased, especially in the aged mice MSCs. When induced to be osteogenic, Osx gene expression and ALP activity declined in the mid-age and aged mice MSCs, while OCN protein secretion deteriorated in the aged mice MSCs.ConclusionsThese findings demonstrate that mouse MSCs changed with their proliferation and osteo-differentiation abilities at different aging stages, and that Bmal1 is related to the normal aging process in MSCs.

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“…Even before the advent of molecular biological tools, there have been clues linking circadian rhythms to bone metabolism. Clinical studies have detected 24‐h oscillations in human serum levels of osteocalcin and alkaline phosphatase, both markers of osteoblast activity, and C‐telopeptide, released during collagen turnover in resorbing bone (21–28) . In a goat mandibular model, osteoblast proliferation markers displayed a circadian expression profile; this became more pronounced by a growth promoting procedure known as distraction osteogenic (29,30) .…”

Section: Discussionmentioning

confidence: 99%

Circadian Oscillation of Gene Expression in Murine Calvarial Bone

Zvonic

Ptitsyn

Kilroy

et al. 2007

Journal of Bone and Mineral Research

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ABSTRACT:The genes encoding the core circadian transcription factors display an oscillating expression profile in murine calvarial bone. More than 26% of the calvarial bone transcriptome exhibits a circadian rhythm, comparable with that observed in brown and white adipose tissues and liver. Thus, circadian mechanisms may directly modulate oxidative phosphorylation and multiple metabolic pathways in bone homeostasis.Introduction: Although circadian rhythms have been associated historically with central regulatory mechanisms, there is emerging evidence that the circadian transcriptional apparatus exists in peripheral tissues. The aim of this study was to determine the presence and extent of circadian oscillation in the transcriptome of murine calvarial bone. Materials and Methods: Cohorts of 8-week-old male AKR/J mice were maintained in a controlled 12-h light:12-h dark cycle on an ad libitum diet for 2 weeks. Groups of three mice were killed every 4 h over a 48-h period. The level of gene expression at successive times-points was determined by quantitative RT-PCR and Affymetrix microarray. Data were analyzed using multiple statistical time series algorithms, including Cosinor, Fisher g-test, and the permutation time test. Results: Both the positive (Bmal1, Npas2) and negative (Cry1, Cry2, Per1, Per2, Per3) elements of the circadian transcriptional apparatus and their immediate downstream targets and mediators (Dbp, Rev-erb␣, Rev-erb␤) exhibited oscillatory expression profiles. Consistent with findings in other tissues, the positive and negative elements were in antiphase relative to each other. More than 26% of the genes present on the microarray displayed an oscillatory profile in calvarial bone, comparable with the levels observed in brown and white adipose tissues and liver; however, only a subset of 174 oscillating genes were shared among all four tissues. Conclusions: Our findings show that the components of the circadian transcriptional apparatus are represented in calvarial bone and display coordinated oscillatory behavior. However, these are not the only genes to display an oscillatory expression profile, which is seen in multiple pathways involving oxidative phosphorylation and lipid, protein, and carbohydrate metabolism.

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Circadian Rhythms in Serum Bone Markers and Their Relation to the Effect of Etidronate in Rats

Cited by 43 publications

References 30 publications

A fluorescence spotlight on the clockwork development and metabolism of bone

A fluorescence spotlight on the clockwork development and metabolism of bone

Age-related BMAL1 change affects mouse bone marrow stromal cell proliferation and osteo-differentiation potential

Circadian Oscillation of Gene Expression in Murine Calvarial Bone

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