Robust Circadian Rhythm and Parathyroid Hormone-Induced Resetting during Hypertrophic Differentiation in ATDC5 Chondroprogenitor Cells

Hosokawa, Tomokazu; Tsuchiya, Yoshiki; Okubo, Naoki; Kunimoto, Tatsuya; Minami, Yoichi; Fujiwara, Hiroyoshi; Umemura, Yasuhiro; Koike, Nobuya; Kubo, Toshikazu; Yagita, Kazuhiro

doi:10.1267/ahc.15025

Cited by 9 publications

(5 citation statements)

References 34 publications

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“…The data presented here suggests that phosphate mineral metabolism controls peripheral circadian functions. Consistent with our studies that lead us to this conclusion are data showing that PTH, which leads to both a hyperphosphatemic state and increases the rate of chondrocyte differentiation, causes an inverse effect of shortening of the clock genes’ diurnal expression cycle in growth plates, fracture callus tissues and murine chondrocytes and chondroprogenitor cells 14 , 15 , 45 , 46 . The interplay between the regulatory mechanisms of mineral metabolism and circadian functions is also supported by multiple research studies in osteoblasts.…”

Section: Discussionsupporting

confidence: 89%

Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm

Noguchi

Hussein

Horowitz

et al. 2018

Sci Rep

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Transcriptomic analysis showed that the central circadian pathway genes had significantly altered expression in fracture calluses from mice fed a low phosphate diet. This led us to hypothesize that phosphate deficiency altered the circadian cycle in peripheral tissues. Analysis of the expression of the central clock genes over a 24–36 hour period in multiple peripheral tissues including fracture callus, proximal tibia growth plate and cardiac tissues after 12 days on a low phosphate diet showed higher levels of gene expression in the hypophosphatemia groups (p < 0.001) and a 3 to 6 hour elongation of the circadian cycle. A comparative analysis of the callus tissue transcriptome genes that were differentially regulated by hypophosphatemia with published data for the genes in bone that are diurnally regulated identified 1879 genes with overlapping differential regulation, which were shown by ontology assessment to be associated with oxidative metabolism and apoptosis. Network analysis of the central circadian pathway genes linked their expression to the up regulated expression of the histone methyltransferase gene EZH2, a gene that when mutated in both humans and mice controls overall skeletal growth. These data suggest that phosphate is an essential metabolite that controls circadian function in both skeletal and non skeletal peripheral tissues and associates its levels with the overall oxidative metabolism and skeletal growth of animals.

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Section: Discussionsupporting

confidence: 89%

Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm

Noguchi

Hussein

Horowitz

et al. 2018

Sci Rep

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“…After collection, the IM and cortex were divided, frozen by liquid nitrogen, and stored in an −80 °C deep freezer until RNA isolations. Total RNA extraction and cDNA synthesis were performed as described previously 53 . The amplification protocol comprised an initial incubation at 95 °C for 10 min and 40 cycles of 95 °C for 15 sec and 60 °C for 1 min, followed by melting curve analysis.…”

Section: Methodsmentioning

confidence: 99%

Robust circadian clock oscillation and osmotic rhythms in inner medulla reflecting cortico-medullary osmotic gradient rhythm in rodent kidney

Hara

Minami

Ohashi

et al. 2017

Sci Rep

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Circadian clocks in mammals function in most organs and tissues throughout the body. Various renal functions such as the glomerular filtration and excretion of electrolytes exhibit circadian rhythms. Although it has been reported that the expression of the clock genes composing molecular oscillators show apparent daily rhythms in rodent kidneys, functional variations of regional clocks are not yet fully understood. In this study, using macroscopic bioluminescence imaging method of the PER2::Luciferase knock-in mouse kidney, we reveal that strong and robust circadian clock oscillation is observed in the medulla. In addition, the osmotic pressure in the inner medulla shows apparent daily fluctuation, but not in the cortex. Quantitative-PCR analysis of the genes contributing to the generation of high osmotic pressure or the water re-absorption in the inner medulla, such as vasopressin receptors (V1aR, V2R), urea transporter (UT-A2) and water channel (Aqp2) show diurnal variations as well as clock genes. Deficiency of an essential clock gene Bmal1 impairs day-night variations of osmotic pressure gradient in the inner medulla, suggesting that circadian clocks in the medulla part of the kidney may regulate the circadian rhythm of cortico-medullary osmotic pressure gradient, and may contribute physiological day-night rhythm of urination.

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“…PTH directly regulates circadian oscillation of the clock genes in chondrocytes ( 101 ) and is able to reset the robust circadian rhythm in chondroprogenitor cells. ( 102 ) This circadian oscillation is not only crucial for bone growth during aging but also important for endochondral bone formation during fracture healing. ( 103 ) Besides, FGF23 expression, which itself depends on the circadian clock, food intake, and sympathetic activity ( 104 ) and phosphate influence skeletal growth in a circadian fashion.…”

Section: Chronobiology Of Osteoporosismentioning

confidence: 99%

Chronobiology and Chronotherapy of Osteoporosis

et al. 2021

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Physiological circadian (ie, 24-hour) rhythms are critical for bone health. Animal studies have shown that genes involved in the intrinsic molecular clock demonstrate potent circadian expression patterns in bone and that genetic disruption of these clock genes results in a disturbed bone structure and quality. More importantly, circulating markers of bone remodeling show diurnal variation in mice as well as humans, and circadian disruption by, eg, working night shifts is associated with the bone remodeling disorder osteoporosis. In this review, we provide an overview of the current literature on rhythmic bone remodeling and its underlying mechanisms and identify critical knowledge gaps. In addition, we discuss novel (chrono)therapeutic strategies to reduce osteoporosis by utilizing our knowledge on circadian regulation of bone.

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Robust Circadian Rhythm and Parathyroid Hormone-Induced Resetting during Hypertrophic Differentiation in ATDC5 Chondroprogenitor Cells

Cited by 9 publications

References 34 publications

Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm

Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm

Robust circadian clock oscillation and osmotic rhythms in inner medulla reflecting cortico-medullary osmotic gradient rhythm in rodent kidney

Chronobiology and Chronotherapy of Osteoporosis

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