A novel strategy for managing plasam phosphate; osteocytes network as a molecular target

• Project/Area Number: 26461253
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: TATSUMI Sawako 徳島大学, 大学院医歯薬学研究部(医学系), 助教 (80420545)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: リン / 骨細胞 / 骨細胞ネットワーク / 慢性腎臓病 / リン代謝 / 無機リン酸

Outline of Final Research Achievements

Hyperphosphatemia is linked to vasclular calcification with chronic kidney disease (CKD) and an independent risk factor for cardiovascular mortality in haemodialysis patients. In CKD patients, plasma phosphate (Pi) control is essential for improving life prognosi.
Osteocytes are known as endocrine cells because osteocytes secrete FGF23 (Fibroblast growth factor 23) as phosphate regulating factors. Osteocytes make osteocytic canaliculi-osteocyte network through dendrites in osteocytic canaliculi to each other. We hypothesized that the osteocyte network controls plasma Pi levels and dietary Pi sensing. The osteocyte network disrupted mice did not respond loading high Pi diet. In osteocyte network disrupted mice, renal fibrosis and ectopic calcification were observed. Thus, we suggested that osteocyte is a sensory cell for dietary Pi loading. We show that maintenance of the number of osteocyte leads to preveting CKD progression and ectopic calcification.

Research Products

• [Journal Article] Regulation of renal phosphate handling:inter-organ communication in health and disease. (2016)
  • Author(s): Tatsumi S, Miyagawa A, Kaneko I, Shiozaki Y, Segawa H, Miyamoto K.
  • Journal Title: J Bone Miner Metab. Volume: 34(1) Issue: 1 Pages: 1-10
  • DOI: 10.1007/s00774-015-0705-z
  • Peer Reviewed / Open Access
• [Journal Article] Control of phosphate balance by the kidney and intestine. (2016)
  • Author(s): Kaneko I, Tatsumi S, Segawa H,Miyamoto KI.
  • Journal Title: Clin Exp Nephrol. Volume: Mar;21 Issue: S1 Pages: 21-26
  • DOI: 10.1007/s10157-016-1359-4
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of inorganic phosphate ion homeostasis: crosstalk kidney and other organs (2016)
  • Author(s): Tatsumi S, Miyamoto K.
  • Journal Title: Folia Pharmacologica Japonica Volume: 147 Issue: 2 Pages: 84-88
  • DOI: 10.1254/fpj.147.84
  • NAID: 130005125652
  • ISSN: 0015-5691, 1347-8397
  • Open Access
• [Journal Article] Niacin and Chronic Kidney Disease (2015)
  • Author(s): Taketani Y, Masuda M, Yamanaka-Okumura H, Tatsumi S, Segawa H, Miyamoto K, Takeda E, Yamamoto H.
  • Journal Title: Journal of Nutritional Science and Vitaminology Volume: 61 Issue: Supplement Pages: S173-S175
  • DOI: 10.3177/jnsv.61.S173
  • NAID: 130005109895
  • ISSN: 0301-4800, 1881-7742
  • Peer Reviewed / Open Access
• [Journal Article] Bone and Nutrition. Sclerostin and bone metabolism. (2015)
  • Author(s): Tatsumi S, Nagamoto K, Ogata M, Miyamoto K.
  • Journal Title: Clin Calcium. Volume: 25（7） Pages: 1043-1047
  • Peer Reviewed / Open Access
• [Journal Article] Genetic diseases of renal phosphate handling. (2015)
  • Author(s): Kaneko I, Segawa H, Tatsumi S, Miyamoto K.
  • Journal Title: Nihon Jinzo Gakkai Shi. Volume: 57（4） Pages: 758-765
  • NAID: 120006847381
  • Open Access
• [Journal Article] Relationship between sodium-dependent phosphate transporter (NaPi-IIc) function and cellular vacuole formation in opossum kidney cells (2015)
  • Author(s): Shiozaki Y, Segawa H, Ohnishi S, Ohi A, Ito N, Kaneko I, Kido S, Tatsumi S, Miyamoto K.
  • Journal Title: The Journal of Medical Investigation Volume: 62 Issue: 3.4 Pages: 209-218
  • DOI: 10.2152/jmi.62.209
  • NAID: 130005099143
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access
• [Journal Article] Effect of dietary components on renal inorganic phosphate (Pi) excretion induced by a Pi-depleted diet. (2014)
  • Author(s): Ohnishi R, Segawa H, Ohmoto T, Sasaki S, Hanazaki A, Mori A, Ikuta K, Furutani J, Kawakami E, Tatsumi S, Hamada Y, Miyamoto K.
  • Journal Title: J Med Invest. Volume: 61(1.2) Pages: 162-170
  • NAID: 130004822704
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Molecular Mechanisms of Cadmium-Induced Fibroblast growth Factor 23 Upregulation in Osteoblast-Like Cells (2014)
  • Author(s): Kido S, Fujihara M, Nomura K, Sasaki S(他8名)
  • Journal Title: Toxicol Sci. Jun Volume: 139(2) Issue: 2 Pages: 301-316
  • DOI: 10.1093/toxsci/kfu043
  • Peer Reviewed / Open Access
• [Journal Article] Sodium-dependent inorganic phosphate transporters and biomineralization. (2014)
  • Author(s): Tatsumi S, Fujii O, Miyagawa A, Miyamoto K.
  • Journal Title: Clin Calcium. Volume: 24(2) Pages: 249-255
  • Acknowledgement Compliant
• [Journal Article] Hepatectomy-Related Hypophosphatemia : A Novel Phosphaturic Factor in the Liver-Kidney Axis (2014)
  • Author(s): Nomura K, Tatsumi S, Miyamoto K(他10名)
  • Journal Title: J Am Soc Nephrol Volume: vol.25, No.4 Issue: 4 Pages: 761-772
  • DOI: 10.1681/asn.2013060569
  • Peer Reviewed / Open Access
• [Presentation] 生体内リン恒常性におけるIntestinal Alkaline Phosphatase(IAP)の役割. (2017)
  • Author(s): 瀬川博子,佐々木祥平,結城志帆子,金子一郎,辰巳佐和子,宮本賢一.
  • Organizer: 第1回CKD‐MBD研究会学術集会・総会.
  • Place of Presentation: コクヨホール東京（東京都品川区）
  • Year and Date: 2017-03-18
• [Presentation] Salivary Pi Handling May Be under the Control of Gastrointestinal Pi Sensing. (2016)
  • Author(s): Kayo Ikuta, Hiroko Segawa, Shihoko Yuki, Ichiro Kaneko, Ai Hanazaki, Toru Fujii, Aoi Kushi, Sawako Tatsumi, Ken-Ichi Miyamoto.
  • Organizer: American Society of Nephrology.Kidney Week2016.
  • Place of Presentation: シカゴ（米国）
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] Hepatectomy-Induced Hypophosphatemia: Mechanisms Underlying Downregulation of Phophate Transport in the Small Intestine. (2016)
  • Author(s): Sawako Tatsumi, Atsumi Miyagawa, Osamu Fujii, Mao Ogata, Ichiro Kaneko, Hiroko Segawa, Keni-Ichi Miyamoto.
  • Organizer: American Society of Nephrology. Kidney Week2016.
  • Place of Presentation: シカゴ（米国）
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] Elucidation of the circadian rhythm in renal phosphate excretion（腎臓リン排泄における概日リズムの解明）. (2016)
  • Author(s): 辰巳佐和子,高濱和子,小柳悟,宮本賢一.
  • Organizer: 第23回日本時間生物学会学術大会.
  • Place of Presentation: 名古屋大学（愛知県名古屋市）
  • Year and Date: 2016-11-12
• [Presentation] リン代謝動態の概日リズム形成機序解明. (2016)
  • Author(s): 高濱和子,辰巳佐和子,宮川淳美,藤井理,新垣友啓,緒方雅央,木下瑛美,金子一郎,瀬川博子,宮本賢一.
  • Organizer: 第49回日本栄養・食糧学会 中国・四国支部大会.
  • Place of Presentation: 徳島大学（徳島県徳島市）
  • Year and Date: 2016-11-12
• [Presentation] 骨と健康寿命の検討について. (2016)
  • Author(s): 辰巳佐和子,藤井理,宮川淳美,宮本賢一.
  • Organizer: 第63回日本栄養改善学会.
  • Place of Presentation: リンクステーションホール青森（青森県青森市）
  • Year and Date: 2016-09-06
• [Presentation] 形態の異なるリン化合物接種に対する生体への影響. (2016)
  • Author(s): 川端優佳,瀬川博子,結城志帆子,中山彰吾,藤井公,生田かよ,花崎愛,野津圭二郎, 西口詩織,金子一郎,辰巳佐和子,宮本賢一.
  • Organizer: 第70回日本栄養・食糧学会大会.
  • Place of Presentation: 神戸ポートピアアホテル（兵庫県神戸市）
  • Year and Date: 2016-05-13
• [Presentation] A Nurr1-dependent phosphaturic hormonegene that is transcriptionally regulated by 1.25-dihydroxyvitamin D. (2016)
  • Author(s): Ichiro Kaneko, Rimpi K Saini, G.Kerr Whitfield, Mikiko Ito,Hiroko Segawa,Sawako Tatsumi,Ken-ichi Miyamoto, Mark R.Haussler, and Peter W.Jurutka.
  • Organizer: XVIII International Congress on Nutrition and Metabolism in Renal Desease(ICRNM2016).
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-04-19
  • Int'l Joint Research
• [Presentation] 骨細胞とミネラル代謝. (2016)
  • Author(s): 辰巳佐和子.
  • Organizer: 第33回ROD-21研究会.
  • Place of Presentation: パレスホテル大宮（埼玉県埼玉市）
  • Year and Date: 2016-01-30
  • Invited
• [Presentation] 骨細胞の減少による胆汁酸代謝異常についての解析. (2016)
  • Author(s): 新垣友啓,辰巳佐和子,緒方雅央,阪口晴菜,安井朗洋,藤井理,永元健太,金子一郎,瀬川博子,宮本賢一.
  • Organizer: 第19会日本病態栄養学会年次学術集会.
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-01-09
• [Presentation] リン血症是正に対するFGF23/Klothoシグナルの解明. (2016)
  • Author(s): 西口詩織,瀬川博子,蓑島さくら,桑原煩治,金子一郎,前田彰,辰巳佐和子,宮本賢一.
  • Organizer: 第19会日本病態栄養学会年次学術集会.
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-01-09
• [Presentation] 脳機能におけるビタミンDの役割について. (2016)
  • Author(s): 金子一郎,Hsieh Jui-Cheng,Whitfield G.Kerr,辰巳佐和子,瀬川博子,宮本賢一,Haussler Mark R,Jurutka Peter W.
  • Organizer: 第19会日本病態栄養学会年次学術集会.
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-01-09
• [Presentation] 骨と健康寿命の検討について. (2016)
  • Author(s): 辰巳佐和子,藤井理,宮川淳美,宮本賢一.
  • Organizer: 第3回日本栄養改善学会四国支部学術総会.
  • Place of Presentation: 四国大学（徳島県徳島市）
• [Presentation] CKD-MBDと食欲の連関. (2016)
  • Author(s): 辰巳佐和子.
  • Organizer: 第3回腎と栄養研究会.
  • Place of Presentation: KPP八重洲ビル（東京都中央区）
• [Presentation] 骨細胞欠損マウスにおけるFGF19ファミリーシグナル経路の破綻. (2015)
  • Author(s): 安井朗洋,辰巳佐和子,宮本賢一.
  • Organizer: 第38回日本分子生物学会年会・第88回日本生化学会大会 合同大会.
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Genetic Deletion of NaPi-2c Rescue Phenotype of klotho Knockout Mice wi thout Improving Severe Hyperphosphat emia. (2015)
  • Author(s): Ai Hanazaki, Hiroko Segawa, Kayo Ikuta, Toru Fujii,Ichiro Kaneko,Shihoko Yuki, Shiori Nishiguchi, Keijiro Notsu,Yuji Shiozaki, Sawako Tatsumi,Ken-ichi Miyamoto.
  • Organizer: American Society of Nephrology Kidney week.
  • Place of Presentation: San Diego Convention center(San Diego CA USA）
  • Year and Date: 2015-11-04
  • Int'l Joint Research
• [Presentation] Klotho and NaPi-2c,double deletionから導くNaPi-2cの重要性. (2015)
  • Author(s): 花崎愛,瀬川博子,福尾真理,金子一郎,辰巳佐和子,宮本賢一.
  • Organizer: 第48回日本栄養・食糧学会中国・四国支部大会.
  • Place of Presentation: メルパルク広島（広島県広島市）
  • Year and Date: 2015-10-31
• [Presentation] 慢性腎臓病による高リン血症改善におけるナイアシンの効果. (2015)
  • Author(s): 宮川淳美,辰巳佐和子,永元健太,宮本賢一.
  • Organizer: 第62回日本栄養改善学会学術総会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2015-09-24
• [Presentation] Clinical Nutrition education in Japanese dietitians. (2015)
  • Author(s): Kenichi Miyamoto, Sawako Tatsumi, Yasuhiro Hamada.
  • Organizer: 第60回日本透析医学会学術集会・総会.
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-06-26
• [Presentation] Niacin and Chronic Kidney Disease. (2015)
  • Author(s): Yutaka Taketani, Masashi Masuda, Hisami Yamanaka-Okumura, Sawako Tatsumi, Ken-ichi Miyamoto,Eiji Takeda, Hironori Yamamoto.
  • Organizer: ACN2015 12th Asian Congress of Nutrition.
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] The role of Na+-dependent Phosphate transporters in the body. (2015)
  • Author(s): Hiroko Segawa, Ichiro Kaneko, Yuji Shiozaki, Sawako Tatsumi, Ken-ichi Miyamoto.
  • Organizer: ACN2015 12th Asian Congress of Nutrition.
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] Bone-kidney axis regulating phosphate homeostasis: Study of osteocyte-ablated mice. (2015)
  • Author(s): Haruna Sakaguchi, Sawako Tatsumi, Mao Ogata, Osamu Fujii, Tomohiro Arakaki, Atsumi Miyagawa,Kenta Nagamoto, Wako Takahama, Yukiko Hirobata, Akihiro Yasui, Ichiro Kaneko, Hiroko Segawa,Ken-ichi Miyamoto.
  • Organizer: ACN2015 12th Asian Congress of Nutrition.
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] Disruption of intestinal alkaline phosphatase (Akp3) affects the phosphate homeostasis. (2015)
  • Author(s): Shihoko Yuki, Hiroko Segawa, Shohei Sasaki, Kayo Ikuta, Ichiro Kaneko, Toru Fujii, Ai Hanazaki,Shiori Nishiguchi, Keijiro Notsu, Eriko Aki, Yuji Shiozaki, Sawako Tatsumi, Ken-ichi Miyamoto.
  • Organizer: ACN2015 12th Asian Congress of Nutrition.
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] 無機リン酸イオン調節の多階層的制御機序解析. (2015)
  • Author(s): 辰巳佐和子.
  • Organizer: 第88会日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] 無機リン酸イオン調節の多階層的制御機序解析. (2015)
  • Author(s): 辰巳佐和子.
  • Organizer: 新学術領域研究「多階層生体機能学」最終成果報告会
  • Place of Presentation: 大阪中之島センター（大阪府大阪市）
  • Year and Date: 2015-03-04 – 2015-03-05
• [Presentation] 骨細胞除去マウスのカルシウム／リン代謝異常解析について. (2014)
  • Author(s): 緒方雅央,辰巳佐和子,藤井理,阪口晴菜,新垣友啓,宮川淳美,永元健太,高濱和子,廣畠佑希子,金子一郎,瀬川博子,宮本賢一.
  • Organizer: 第47回日本栄養・食糧学会 中国・四国支部大会
  • Place of Presentation: 四国大学交流プラザ（徳島県徳島市）
  • Year and Date: 2014-11-15 – 2014-11-16
• [Presentation] Inorganic Phosphate Handling in Salivary Glands. (2014)
  • Author(s): Ikuta K, Segawa H, Sasaki S, Kaneko I. Shiozaki Y, Tatsumi S, Miyamoto K.
  • Organizer: American Society of Nephrology （米国腎臓学会)
  • Place of Presentation: ﾍﾟﾝｼﾙﾊﾞﾆｱｺﾝﾍﾞﾝｼｮﾝｾﾝﾀｰ(米国ﾌｨﾗﾃﾞﾙﾌｨｱ）
  • Year and Date: 2014-11-11 – 2014-11-16
• [Presentation] 肝臓切除に伴う低リン血症発症機構の解明：ニコチンアミドホスホリボシルトランスフェラーゼ（Nampt）を介した全身性リン代謝制御機構についての検討. (2014)
  • Author(s): 辰巳佐和子,野村憲吾,宮川淳美,永元健太,瀬川博子,宮本賢一.
  • Organizer: 第32回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2014-07-24 – 2014-07-26
• [Presentation] ニコチンアミドホスホリボシルトランスフェラーゼ（Nampt）を介した全身性リン代謝制御機構についての検討. (2014)
  • Author(s): 辰巳佐和子,野村憲吾,宮川淳美,永元健太,藤井理,瀬川博子,宮本賢一.
  • Organizer: 第57回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-07-04 – 2014-07-06
  • Invited
• [Presentation] 骨細胞の機能と異常. (2014)
  • Author(s): 辰巳佐和子,藤井理,宮本賢一.
  • Organizer: 第57回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] 骨細胞特異的死滅マウスの骨小腔基質溶解における微細構造学的検索. (2014)
  • Author(s): 齋藤直朗,李敏啓,辰巳佐和子,池田恭治,網塚憲生,小林正治.
  • Organizer: 第34回日本骨形態計測学会
  • Place of Presentation: さっぽろ芸文館（北海道札幌市）
  • Year and Date: 2014-06-12 – 2014-06-14
• [Presentation] NAD合成律速酵素Namptを介したリン代謝制御機構. (2014)
  • Author(s): 宮川淳美,辰巳佐和子,野村憲吾,永元健太,瀬川博子,宮本賢一.
  • Organizer: 第68回日本栄養・食糧学会大会
  • Place of Presentation: 酪農学園大学（北海道江別市）
  • Year and Date: 2014-05-30 – 2014-06-01
• [Book] 腎と透析診療方針2016,腎と透析vol80増刊号. (2016)
  • Author(s): 金子一郎,瀬川博子,辰巳佐和子,宮本賢一.
  • Publisher: 東京医学社.
• [Book] Annual Review2016. (2016)
  • Author(s): 辰巳佐和子, 宮川淳美, 宮本賢一.
  • Total Pages: 201
  • Publisher: 中外医薬社.
• [Book] 腎臓内科・泌尿器科2（6） (2015)
  • Author(s): 金子一郎, 瀬川博子, 辰巳佐和子, 宮本賢一.
  • Total Pages: 628
  • Publisher: 科学評論社.
• [Book] 腎と骨代謝.Vol28 No1 (2015)
  • Author(s): 辰巳佐和子,藤井理,阪口晴菜,緒方雅央,新垣友啓,宮本賢一.
  • Total Pages: 78
  • Publisher: 日本メディカルセンター
• [Book] Osteo Lipid Vascular ＆Endocrinology―骨代謝と生活習慣病の連関―2015.2Vol.5 No.1 (2015)
  • Author(s): 辰巳佐和子,宮本賢一.
  • Total Pages: 68
  • Publisher: メディカルレビュー社
• [Book] 透析医学 (2014)
  • Author(s): 辰巳佐和子,瀬川博子,宮本賢一.
  • Total Pages: 719
  • Publisher: 医薬ジャーナル社
• [Book] Drug Delivery System Vol. 29(2014) No. 2 (2014)
  • Author(s): 辰巳佐和子,金子一郎,瀬川博子,宮本賢一.
  • Total Pages: 469
  • Publisher: 日本DDS学会