Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin
Many studies have investigated the actions of melatonin on osteoblasts and osteoclasts. However, the underlying mechanisms, especially regarding osteocyte function, remain largely unknown. Therefore, this study aimed to clarify the underlying mechanisms of melatonin action on bone tissue via osteocy...
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Veröffentlicht in: | Journal of endocrinology 2019-08, Vol.242 (2), p.13-23 |
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creator | Nakano, Masaki Ikegame, Mika Igarashi-Migitaka, Junko Maruyama, Yusuke Suzuki, Nobuo Hattori, Atsuhiko |
description | Many studies have investigated the actions of melatonin on osteoblasts and osteoclasts. However, the underlying mechanisms, especially regarding osteocyte function, remain largely unknown. Therefore, this study aimed to clarify the underlying mechanisms of melatonin action on bone tissue via osteocyte function. Chick calvariae were employed as a model. In ovo injection of melatonin (5, 50 and 500 µg) dose-dependently decreased the mRNA expression levels of cathepsin K and matrix metalloproteinase 9 (MMP9) in chick calvariae without affecting the expression levels of receptor activator of NF-κB ligand or osteoprotegerin. Surprisingly enough, the expression of calcitonin mRNA in chick calvariae was significantly raised. After 3 days of in vitro treatment of melatonin (10−7 and 10−5 M) on newly hatched chick calvariae, both calcitonin mRNA expression in calvariae and the concentration of calcitonin in cultured medium were augmented in a dose-dependent manner, coincident with the decreased mRNA expression levels of cathepsin K and MMP9. Immunohistochemical analyses revealed expression of melatonin receptors and calcitonin by osteocytes buried in bone matrix. Moreover, the mRNA expression levels of melatonin receptors, calcitonin and sclerostin (a marker of osteocyte), were strongly and positively correlated. In conclusion, we demonstrated the expression of melatonin receptors and calcitonin expression in osteocytes for the first time and suggest a new mechanism underlying the suppressive effect of melatonin on osteoclasts via upregulation of calcitonin secretion by osteocytes. |
doi_str_mv | 10.1530/JOE-18-0707 |
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However, the underlying mechanisms, especially regarding osteocyte function, remain largely unknown. Therefore, this study aimed to clarify the underlying mechanisms of melatonin action on bone tissue via osteocyte function. Chick calvariae were employed as a model. In ovo injection of melatonin (5, 50 and 500 µg) dose-dependently decreased the mRNA expression levels of cathepsin K and matrix metalloproteinase 9 (MMP9) in chick calvariae without affecting the expression levels of receptor activator of NF-κB ligand or osteoprotegerin. Surprisingly enough, the expression of calcitonin mRNA in chick calvariae was significantly raised. After 3 days of in vitro treatment of melatonin (10−7 and 10−5 M) on newly hatched chick calvariae, both calcitonin mRNA expression in calvariae and the concentration of calcitonin in cultured medium were augmented in a dose-dependent manner, coincident with the decreased mRNA expression levels of cathepsin K and MMP9. Immunohistochemical analyses revealed expression of melatonin receptors and calcitonin by osteocytes buried in bone matrix. Moreover, the mRNA expression levels of melatonin receptors, calcitonin and sclerostin (a marker of osteocyte), were strongly and positively correlated. In conclusion, we demonstrated the expression of melatonin receptors and calcitonin expression in osteocytes for the first time and suggest a new mechanism underlying the suppressive effect of melatonin on osteoclasts via upregulation of calcitonin secretion by osteocytes.</description><identifier>ISSN: 0022-0795</identifier><identifier>EISSN: 1479-6805</identifier><identifier>DOI: 10.1530/JOE-18-0707</identifier><identifier>PMID: 31042672</identifier><language>eng</language><publisher>England: Bioscientifica Ltd</publisher><subject>Animals ; Avian Proteins - genetics ; Avian Proteins - metabolism ; Calcitonin - genetics ; Calcitonin - metabolism ; Cells, Cultured ; Chick Embryo ; Chickens ; Gene Expression Regulation, Developmental - drug effects ; Melatonin - administration & dosage ; Melatonin - pharmacology ; Osteoclasts - cytology ; Osteoclasts - drug effects ; Osteoclasts - metabolism ; Osteocytes - cytology ; Osteocytes - drug effects ; Osteocytes - metabolism ; Receptors, Melatonin - genetics ; Receptors, Melatonin - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Skull - cytology ; Skull - drug effects ; Skull - metabolism ; Up-Regulation - drug effects</subject><ispartof>Journal of endocrinology, 2019-08, Vol.242 (2), p.13-23</ispartof><rights>2019 Society for Endocrinology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b434t-1f448208821536df28d93c69f3c2965fda8cb20bcb735b1d73237efdcb5d4ffe3</citedby><cites>FETCH-LOGICAL-b434t-1f448208821536df28d93c69f3c2965fda8cb20bcb735b1d73237efdcb5d4ffe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31042672$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nakano, Masaki</creatorcontrib><creatorcontrib>Ikegame, Mika</creatorcontrib><creatorcontrib>Igarashi-Migitaka, Junko</creatorcontrib><creatorcontrib>Maruyama, Yusuke</creatorcontrib><creatorcontrib>Suzuki, Nobuo</creatorcontrib><creatorcontrib>Hattori, Atsuhiko</creatorcontrib><title>Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin</title><title>Journal of endocrinology</title><addtitle>J Endocrinol</addtitle><description>Many studies have investigated the actions of melatonin on osteoblasts and osteoclasts. However, the underlying mechanisms, especially regarding osteocyte function, remain largely unknown. Therefore, this study aimed to clarify the underlying mechanisms of melatonin action on bone tissue via osteocyte function. Chick calvariae were employed as a model. In ovo injection of melatonin (5, 50 and 500 µg) dose-dependently decreased the mRNA expression levels of cathepsin K and matrix metalloproteinase 9 (MMP9) in chick calvariae without affecting the expression levels of receptor activator of NF-κB ligand or osteoprotegerin. Surprisingly enough, the expression of calcitonin mRNA in chick calvariae was significantly raised. After 3 days of in vitro treatment of melatonin (10−7 and 10−5 M) on newly hatched chick calvariae, both calcitonin mRNA expression in calvariae and the concentration of calcitonin in cultured medium were augmented in a dose-dependent manner, coincident with the decreased mRNA expression levels of cathepsin K and MMP9. Immunohistochemical analyses revealed expression of melatonin receptors and calcitonin by osteocytes buried in bone matrix. Moreover, the mRNA expression levels of melatonin receptors, calcitonin and sclerostin (a marker of osteocyte), were strongly and positively correlated. In conclusion, we demonstrated the expression of melatonin receptors and calcitonin expression in osteocytes for the first time and suggest a new mechanism underlying the suppressive effect of melatonin on osteoclasts via upregulation of calcitonin secretion by osteocytes.</description><subject>Animals</subject><subject>Avian Proteins - genetics</subject><subject>Avian Proteins - metabolism</subject><subject>Calcitonin - genetics</subject><subject>Calcitonin - metabolism</subject><subject>Cells, Cultured</subject><subject>Chick Embryo</subject><subject>Chickens</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>Melatonin - administration & dosage</subject><subject>Melatonin - pharmacology</subject><subject>Osteoclasts - cytology</subject><subject>Osteoclasts - drug effects</subject><subject>Osteoclasts - metabolism</subject><subject>Osteocytes - cytology</subject><subject>Osteocytes - drug effects</subject><subject>Osteocytes - metabolism</subject><subject>Receptors, Melatonin - genetics</subject><subject>Receptors, Melatonin - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Skull - cytology</subject><subject>Skull - drug effects</subject><subject>Skull - metabolism</subject><subject>Up-Regulation - drug effects</subject><issn>0022-0795</issn><issn>1479-6805</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLxDAURoMozji6ci9dClLNq02yFBlfDMxCXYckTSDSNrVJB-bfm3FGl8KFCx-Hj3sPAJcI3qKKwLvX9bJEvIQMsiMwR5SJsuawOgZzCDHOuahm4CzGTwhRhRg5BTOCIMU1w3OwfpuGYbQx-o0trHPWpCK4orOtSqH3fRHyxGSDaVVMhZt6k3zONl4d8m2yhVGt8T_8OThxqo324rAX4ONx-f7wXK7WTy8P96tSU0JTiRylHEPOcX6hbhzmjSCmFo4YLOrKNYobjaE2mpFKo4YRTJh1jdFVQ_OVZAGu973DGL4mG5PsfDS2bVVvwxQlxogLISgkGb3Zo2YMMY7WyWH0nRq3EkG5MyizQYm43BnM9NWheNKdbf7YX2UZQHtA-xCNt33yzhv1b-k3Uod84g</recordid><startdate>201908</startdate><enddate>201908</enddate><creator>Nakano, Masaki</creator><creator>Ikegame, Mika</creator><creator>Igarashi-Migitaka, Junko</creator><creator>Maruyama, Yusuke</creator><creator>Suzuki, Nobuo</creator><creator>Hattori, Atsuhiko</creator><general>Bioscientifica Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201908</creationdate><title>Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin</title><author>Nakano, Masaki ; Ikegame, Mika ; Igarashi-Migitaka, Junko ; Maruyama, Yusuke ; Suzuki, Nobuo ; Hattori, Atsuhiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b434t-1f448208821536df28d93c69f3c2965fda8cb20bcb735b1d73237efdcb5d4ffe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Avian Proteins - genetics</topic><topic>Avian Proteins - metabolism</topic><topic>Calcitonin - genetics</topic><topic>Calcitonin - metabolism</topic><topic>Cells, Cultured</topic><topic>Chick Embryo</topic><topic>Chickens</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>Melatonin - administration & dosage</topic><topic>Melatonin - pharmacology</topic><topic>Osteoclasts - cytology</topic><topic>Osteoclasts - drug effects</topic><topic>Osteoclasts - metabolism</topic><topic>Osteocytes - cytology</topic><topic>Osteocytes - drug effects</topic><topic>Osteocytes - metabolism</topic><topic>Receptors, Melatonin - genetics</topic><topic>Receptors, Melatonin - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Skull - cytology</topic><topic>Skull - drug effects</topic><topic>Skull - metabolism</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nakano, Masaki</creatorcontrib><creatorcontrib>Ikegame, Mika</creatorcontrib><creatorcontrib>Igarashi-Migitaka, Junko</creatorcontrib><creatorcontrib>Maruyama, Yusuke</creatorcontrib><creatorcontrib>Suzuki, Nobuo</creatorcontrib><creatorcontrib>Hattori, Atsuhiko</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nakano, Masaki</au><au>Ikegame, Mika</au><au>Igarashi-Migitaka, Junko</au><au>Maruyama, Yusuke</au><au>Suzuki, Nobuo</au><au>Hattori, Atsuhiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin</atitle><jtitle>Journal of endocrinology</jtitle><addtitle>J Endocrinol</addtitle><date>2019-08</date><risdate>2019</risdate><volume>242</volume><issue>2</issue><spage>13</spage><epage>23</epage><pages>13-23</pages><issn>0022-0795</issn><eissn>1479-6805</eissn><abstract>Many studies have investigated the actions of melatonin on osteoblasts and osteoclasts. However, the underlying mechanisms, especially regarding osteocyte function, remain largely unknown. Therefore, this study aimed to clarify the underlying mechanisms of melatonin action on bone tissue via osteocyte function. Chick calvariae were employed as a model. In ovo injection of melatonin (5, 50 and 500 µg) dose-dependently decreased the mRNA expression levels of cathepsin K and matrix metalloproteinase 9 (MMP9) in chick calvariae without affecting the expression levels of receptor activator of NF-κB ligand or osteoprotegerin. Surprisingly enough, the expression of calcitonin mRNA in chick calvariae was significantly raised. After 3 days of in vitro treatment of melatonin (10−7 and 10−5 M) on newly hatched chick calvariae, both calcitonin mRNA expression in calvariae and the concentration of calcitonin in cultured medium were augmented in a dose-dependent manner, coincident with the decreased mRNA expression levels of cathepsin K and MMP9. Immunohistochemical analyses revealed expression of melatonin receptors and calcitonin by osteocytes buried in bone matrix. Moreover, the mRNA expression levels of melatonin receptors, calcitonin and sclerostin (a marker of osteocyte), were strongly and positively correlated. In conclusion, we demonstrated the expression of melatonin receptors and calcitonin expression in osteocytes for the first time and suggest a new mechanism underlying the suppressive effect of melatonin on osteoclasts via upregulation of calcitonin secretion by osteocytes.</abstract><cop>England</cop><pub>Bioscientifica Ltd</pub><pmid>31042672</pmid><doi>10.1530/JOE-18-0707</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Avian Proteins - genetics Avian Proteins - metabolism Calcitonin - genetics Calcitonin - metabolism Cells, Cultured Chick Embryo Chickens Gene Expression Regulation, Developmental - drug effects Melatonin - administration & dosage Melatonin - pharmacology Osteoclasts - cytology Osteoclasts - drug effects Osteoclasts - metabolism Osteocytes - cytology Osteocytes - drug effects Osteocytes - metabolism Receptors, Melatonin - genetics Receptors, Melatonin - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Skull - cytology Skull - drug effects Skull - metabolism Up-Regulation - drug effects |
title | Suppressive effect of melatonin on osteoclast function via osteocyte calcitonin |
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