Circadian Rhythm of Osteocalcin in the Maxillomandibular                Complex

Gafni, Yossi; Ptitsyn, Andrey A.; Zilberman, Yoram; Pelled, Gadi; Gimble, Jeffrey M.; Gazit, Dan

doi:10.1177/0022034508328012

Cited by 33 publications

(29 citation statements)

References 29 publications

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“…It is composed of a positive and negative regulatory feedback loop that is entrained by external zeitgebers (temporal cues), such as the sun, with the positive arm consisting of the transcription factors BMAL1 and CLOCK, and the negative arm consisting of the transcription factors PERIODS (PER) and CRYPTOCHROMES [115]. Increasing evidence indicates that circadian clocks also regulate skeletal homeostasis [116] [117]. Interestingly, some chondrocyte-specific genes, such as Col2a1 and Col10a1 , are expressed in a diurnal pattern along with the core clock genes in chondrogenic ATDC5 cells as well as in articular cartilage and growth plates [118] [119].…”

Section: The Circadian Clockmentioning

confidence: 99%

Signaling pathways regulating cartilage growth plate formation and activity

Samsa

Zhou

2017

Seminars in Cell & Developmental Biology

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The growth plate is a highly specialized and dynamic cartilage structure that serves many essential functions in skeleton patterning, growth and endochondral ossification in developing vertebrates. Major signaling pathways initiated by classical morphogens and by other systemic and tissuespecific factors are intimately involved in key aspects of growth plate development. As a corollary of these essential functions, disturbances in these pathways due to mutations or environmental factors lead to severe skeleton disorders. Here, we review these pathways and the most recent progress made in understanding their roles in chondrocyte differentiation in growth plate development and activity. Furthermore, we discuss newly uncovered pathways involved in growth plate formation, including mTOR, the circadian clock, and the COP9 signalosome.

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Section: The Circadian Clockmentioning

confidence: 99%

Signaling pathways regulating cartilage growth plate formation and activity

Samsa

Zhou

2017

Seminars in Cell & Developmental Biology

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“…However fluctuations in total OC levels, as seen with circadian rhythm, aging and diabetes, are to some extent associated with changes in metabolism. In mice (which are nocturnal), osteocalcin expression is highest during the day when they are sleeping (and insulin sensitivity is low) (54) and then decreases during the night (when glucose and insulin increase) (55). This is consistent with the human activity pattern of low levels of OC in the morning and peak levels at night (55–57).…”

Section: Bone Regulation Of Metabolism: Evidence From Rodent Modelsmentioning

confidence: 99%

Bone and glucose metabolism: A two-way street

Motyl

McCabe

Schwartz

2010

Archives of Biochemistry and Biophysics

100

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Evidence from rodent models indicates that undercarboxylated osteocalcin (ucOC), a product of osteoblasts, is a hormone affecting insulin production by the pancreas and insulin sensitivity in peripheral tissues, at least in part through enhanced secretion of adiponectin from adipocytes. Clinical research to test whether this relationship is found in humans is just beginning to emerge. Cross-sectional studies confirm associations between total osteocalcin (OC), ucOC and glucose metabolism but cannot distinguish causality. To date, longitudinal studies have not provided a consistent picture of the effects of ucOC or OC on fasting glucose and insulin sensitivity. Further exploration into the physiological and mechanistic effects of ucOC and OC, in rodent models and clinical studies, is necessary to determine to what extent the skeleton regulates energy metabolism in humans.

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“…Gafni et al [123] tested the hypothesis that peripheral circadian mechanisms contribute to the transcriptional regulation of osteocalcin. They used a human osteocalcin promoter/luciferase reporter (hOC-Luc) transgenic murine model that was previously validated in vivo for serial non-invasive bioluminescence imaging [124].…”

Section: Post-genomic Approaches For Evaluating Circadian Rhythm In Bonementioning

confidence: 99%

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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Circadian Rhythm of Osteocalcin in the Maxillomandibular Complex

Abstract: A supplemental appendix to this article is published electronically only at

Cited by 33 publications

References 29 publications

Signaling pathways regulating cartilage growth plate formation and activity

Signaling pathways regulating cartilage growth plate formation and activity

Bone and glucose metabolism: A two-way street

A fluorescence spotlight on the clockwork development and metabolism of bone

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