α-Melanocyte-stimulating hormone promotes bone resorption resulting from increased osteoblastic and osteoclastic activities in goldfish

Ishizu, Hidenori; Sekiguchi, Toshio; Ikari, Takahiro; Kitamura, Kei-ichiro; Kitani, Yoichiro; Endo, Masato; Urata, Makoto; Kinoshita, Yasuko; Hattori, Atsuhiko; Srivastav, Ajai K.; Mishima, Hiroyuki; Mizusawa, Kanta; Takahashi, Akiyoshi; Suzuki, Nobuo

doi:10.1016/j.ygcen.2018.03.020

Cited by 7 publications

(5 citation statements)

References 35 publications

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“…Total RNA isolation and cDNA synthesis were performed using a kit (Qiagen GmbH) . Primers used for quantitative real‐time PCR (qPCR) are listed in Table .…”

Section: Methodsmentioning

confidence: 99%

Melatonin is a potential drug for the prevention of bone loss during space flight

Ikegame

Hattori

Tabata

et al. 2019

Journal of Pineal Research

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Astronauts experience osteoporosis‐like loss of bone mass because of microgravity conditions during space flight. To prevent bone loss, they need a riskless and antiresorptive drug. Melatonin is reported to suppress osteoclast function. However, no studies have examined the effects of melatonin on bone metabolism under microgravity conditions. We used goldfish scales as a bone model of coexisting osteoclasts and osteoblasts and demonstrated that mRNA expression level of acetylserotonin O‐methyltransferase, an enzyme essential for melatonin synthesis, decreased significantly under microgravity. During space flight, microgravity stimulated osteoclastic activity and significantly increased gene expression for osteoclast differentiation and activation. Melatonin treatment significantly stimulated Calcitonin (an osteoclast‐inhibiting hormone) mRNA expression and decreased the mRNA expression of receptor activator of nuclear factor κB ligand (a promoter of osteoclastogenesis), which coincided with suppressed gene expression levels for osteoclast functions. This is the first study to report the inhibitory effect of melatonin on osteoclastic activation by microgravity. We also observed a novel action pathway of melatonin on osteoclasts via an increase in CALCITONIN secretion. Melatonin could be the source of a potential novel drug to prevent bone loss during space flight.

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“…Total RNA isolation and cDNA synthesis were performed using a kit (Qiagen GmbH) . Primers used for quantitative real‐time PCR (qPCR) are listed in Table .…”

Section: Methodsmentioning

confidence: 99%

Melatonin is a potential drug for the prevention of bone loss during space flight

Ikegame

Hattori

Tabata

et al. 2019

Journal of Pineal Research

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“…We previously indicated that a-MSH functions in scales and promotes bone resorption in goldfish (Ishizu et al 2018). In ontogenic scales, the calcium content decreased (Fig.…”

Section: Regenerating Scales Ontogenic Scalesmentioning

confidence: 82%

“…During scale regeneration, both osteoblastic and osteoclastic activities in regenerating scales were higher than those in ontogenic scales (Yoshikubo et al 2005). As a-MSH induced hypercalcemia (Ishizu et al 2018), we strongly believe that a-MSH involves calcium metabolism related to scale regeneration.…”

Section: Introductionmentioning

confidence: 86%

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α-Melanocyte-stimulating hormone directly increases the plasma calcitonin level and involves calcium metabolism in goldfish

et al. 2018

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The effects of a-melanocyte-stimulating hormone (a-MSH) on calcium metabolism were examined with goldfish. The scales on the left side of goldfish bodies were removed to allow the regeneration of scales under anesthesia. Thereafter, the influences of a-MSH injection (low dose: 0.1 lg/g body weight; high dose: 1 lg/g body weight) on plasma calcitonin (calcium-regulating hormone) and the calcium content of the scales were investigated. Ten days after removing the scales, we measured the plasma calcitonin and calcium content of both regenerating scales on the left side and ontogenic scales on the right side. At both doses of a-MSH injection, plasma calcitonin concentrations in the a-MSH-treated group were significantly higher than those in the control group. The mRNA expressions of a-MSH-receptors were detected in the ultimobranchial glands (secretory organ of calcitonin), indicating that a-MSH directly functions in ultimobranchial glands and promotes calcitonin secretion. Furthermore, we found that the calcium content of regenerating scales in a-MSHtreated goldfish was higher than that in control goldfish, while the calcium content of ontogenic scales on the right side was significantly decreased by a-MSH injection. There was a significant co-relationship between plasma calcitonin and the calcium content of regenerating scales. The mRNA expression of calcitonin receptors in regenerating scales was remarkably higher than that in ontogenic scales. These results imply that calcitonin functions to promote scale regeneration resulting from the inhibition of bone resorption because

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“…Quantitative real-time PCR. Isolation of total RNA and cDNA synthesis were performed using kits (Qiagen GmbH, Hilden, Germany) in accordance with the manufacturer's instructions (Ishizu et al 2018). Each quantitative real-time PCR reaction was performed using real-time PCR apparatus (Mx3000p™; Stratagene, La Jolla, CA, USA).…”

Section: Space Experiments On the International Space Stationmentioning

confidence: 99%

Expression of sclerostin in the regenerating scales of goldfish and its increase under microgravity during space flight

et al. 2020

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Osteocytes, osteoblasts (bone-forming cells), and osteoclasts (bone-resorbing cells) are the primary types of cells that regulate bone metabolism in mammals. Sclerostin produced in bone cells activates osteoclasts, inhibiting bone formation; excess production of sclerostin, therefore, leads to the loss of bone mass. Fish scales have been reported to have morphological and functional similarities to mammalian bones, making them a useful experimental system for analyzing vertebrate bone metabolism in vitro. However, whether fish scales contain cells producing sclerostin and/or osteocytes has not been determined. The current study demonstrated, for the first time, that sclerostin-containing cells exist in goldfish scales. Analysis of the distribution and shape of sclerostin-expressing cells provided evidence that osteoblasts produce sclerostin in goldfish scales. Furthermore, our results found that osteocyte-like cells exist in goldfish scales, which also produce sclerostin. Finally, we demonstrated that microgravity in outer space increased the level of sclerostin in the scales of goldfish, a finding suggesting that the induction of sclerostin is the mechanism underlying the activation of osteoclasts under microgravity.

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α-Melanocyte-stimulating hormone promotes bone resorption resulting from increased osteoblastic and osteoclastic activities in goldfish

Cited by 7 publications

References 35 publications

Melatonin is a potential drug for the prevention of bone loss during space flight

Melatonin is a potential drug for the prevention of bone loss during space flight

α-Melanocyte-stimulating hormone directly increases the plasma calcitonin level and involves calcium metabolism in goldfish

Expression of sclerostin in the regenerating scales of goldfish and its increase under microgravity during space flight

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