Development of a novel method using macrophage-activated for therapy against chronic muscle pain

• Project/Area Number: 24390429
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Prosthetic dentistry
• Research Institution: Tohoku University
• Principal Investigator: TSUCHIYA MASAHIRO 東北大学, 歯学研究科(研究院), 大学院非常勤講師 (60372322)
• Co-Investigator(Kenkyū-buntansha): SASAKI Keiichi 東北大学, 大学院歯学研究科, 教授 (30178644) ; HAGIWARA Yoshihiro 東北大学, 大学院医学研究科, 准教授 (90436139) ; KUROISHI Yoshinobu 東北大学, 大学院歯学研究科, 助教 (30400261)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
• Keywords: 筋疲労 / 顎関節症 / IL-1 / マクロファージ / 糖代謝 / 索状硬結 / 慢性筋痛

Outline of Final Research Achievements

Pathological mechanism of chronic muscle pain associated with temporomandibular joint disease (TMD) is still unclear. Using a unique masticatory model, we examined whether macrophages (Mφ) plays roles to recover from muscle fatigue. The masticatory activity didn't increase the number of Mφ in masseter muscle. On the other hand, Mφ depletion by the administration of clodronate-liposome (i.v.) significantly decrease the masticatory-like behavior. In addition, the decrease of IL-1β expression level in the masseter followed by the impairment of IL-6 induction have been observed. Interestingly, we also confirmed that the failure of glucose uptake in skeletal muscle tissues. Our data also underscore the importance of Mφ in IL-1-mediated local interplay between autocrine myokines including IL-6 and paracrine cytokines in active skeletal muscles. This interplay is directly involved in MM performance and fatigability, perhaps mediated through maintaining muscular glucose homeostasis.

Research Products

• [Journal Article] Influence of living environments and working status on low back pain for survivors of the Great East Japan Earthquake. (2016)
  • Author(s): Hagiwara Y, Yabe Y, Sugawara Y, Sato M, Watanabe T, Kanazawa K, Sonofuchi K, Koide M, Sekiguchi T, Tsuchiya M, Tsuji I, Itoi E.
  • Journal Title: J Orthop Sci. Volume: 21 Issue: 2 Pages: 138-142
  • DOI: 10.1016/j.jos.2015.12.015
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Wnt3a signaling induces murine dental follicle cells to differentiate into cementoblastic/osteoblastic cells via an osterix-dependent pathway. (2015)
  • Author(s): Nemoto, E., Sakisaka, M., Tsuchiya, M., Tamura, M., Nakamura, T., Shimonishi, M., and Shimauchi
  • Journal Title: Journal of Periodontal Research Volume: 51(2) Issue: 2 Pages: 164-174
  • DOI: 10.1111/jre.12294
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Involvement of IL-1 in the Maintenance of Masseter Muscle Activity and Glucose Homeostasis. (2015)
  • Author(s): Chiba K, Tsuchiya M, Koide M, Hagiwara Y, Sasaki K, Hattori Y, Watanabe M, Sugawara S, Kanzaki M, Endo Y.
  • Journal Title: PLoS One Volume: 10 (11):e0143635 Issue: 11 Pages: e0143635-e0143635
  • DOI: 10.1371/journal.pone.0143635
  • Peer Reviewed / Open Access
• [Journal Article] Periodontal Disease Is Associated with Insomnia among Victims of the Great East Japan Earthquake: A Panel Study Initiated Three Months after the Disaster. (2015)
  • Author(s): Tsuchiya M, Aida J, Hagiwara Y, Sugawara Y, Tomata Y, Sato M, Watanabe T, Tomita H, Nemoto E, Watanabe M, Osaka K, Tsuji I.
  • Journal Title: Tohoku J Exp Med. Volume: 237 Issue: 2 Pages: 83-90
  • DOI: 10.1620/tjem.237.83
  • NAID: 130005099125
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of peripheral artemin signaling in tongue pain: possible mechanism in burning mouth syndrome. (2015)
  • Author(s): Shinoda M, Takeda M, Honda K, Maruno M, Katagiri A, Satoh-Kuriwada S, Shoji N, Tsuchiya M, Iwata K
  • Journal Title: Pain Volume: 156 Issue: 12 Pages: 2528-2537
  • DOI: 10.1097/j.pain.0000000000000322
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Wnt5a attenuates canonical Wnt-induced alkaline phosphatase expression in dental follicle cells. (2015)
  • Author(s): Sakisaka, Y., Tsuchiya, M., Nakamura, T., Tamura, M., Shimauchi, H., and Nemoto, E.
  • Journal Title: Experimental Cell Research Volume: 336(1) Issue: 1 Pages: 85-93
  • DOI: 10.1016/j.yexcr.2015.06.013
  • Peer Reviewed
• [Journal Article] Preventing effects of joint contracture by high molecular weight hyaluronan injections in a rat immobilized knee model. (2015)
  • Author(s): Kanazawa K, Hagiwara Y, Tsuchiya M, Yabe Y, Sonofuchi K, Koide M, Sekiguchi T, Itaya N, Ando A, Saijo Y, Itoi E.
  • Journal Title: Int J Clin Exp Pathol. Volume: 8 Pages: 3426-3440
  • Peer Reviewed / Open Access
• [Journal Article] Expression of umami-taste-related genesin the tongue: a pilot study for genetic taste diagnosis (2015)
  • Author(s): Shoji N, Kaneta N, Satoh-Kuriwada S, Tsuchiya M, Hashimoto N, Uneyama H, Kawai M, Sasano T
  • Journal Title: Oral Dis. Volume: 21 Issue: 6 Pages: 801-806
  • DOI: 10.1111/odi.12350
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chondrogenic and fibrotic process in the ligamentum flavum of patients with lumbar spinal canal stenosis. (2015)
  • Author(s): Yabe Y, Hagiwara Y, Ando A, Tsuchiya M, Minowa T, Takemura T, Honda M, Hatori K, Sonofuchi K, Kanazawa K, Koide M, Sekiguchi T, Itoi E.
  • Journal Title: Spine Volume: 40 Issue: 7 Pages: 429-435
  • DOI: 10.1097/brs.0000000000000795
  • Peer Reviewed
• [Journal Article] Simultaneous evaluation of articular cartilage and subchondral bone from immobilized knee in rats by photoacoustic imaging system. (2015)
  • Author(s): Hagiwara Y, Izumi T, Yabe Y, Sato M, Sonofuchi K, Kanazawa K, Koide M, Saijo Y, Itoi E.
  • Journal Title: J Orthop Sci. Volume: 20 Issue: 2 Pages: 397-402
  • DOI: 10.1007/s00776-014-0692-2
  • Peer Reviewed / Open Access
• [Journal Article] Biomechanical Evaluation of Ti-Nb-Sn Alloy Implants with a Low Young's Modulus. (2015)
  • Author(s): Takahashi K, Shiraishi N, Ishiko-Uzuka R, Anada T, Suzuki O, Masumoto H, Sasaki K.
  • Journal Title: Int J Mol Sci. Volume: 16 Issue: 3 Pages: 5779-5788
  • DOI: 10.3390/ijms16035779
  • Peer Reviewed / Open Access
• [Journal Article] Long-term feeding on powdered food causes hyperglycemia and signs of systemic illness in mice. (2014)
  • Author(s): Tsuchiya M, Niijima-Yaoita F, Yoneda H, Chiba K, Tsuchiya S, Hagiwara Y, Sasaki K, Sugawara S, Endo Y, Tan-No K, Watanabe M.
  • Journal Title: Life Sci. Volume: 103 Issue: 1 Pages: 8-14
  • DOI: 10.1016/j.lfs.2014.03.022
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Resin monomers act as adjuvants in Ni-induced allergic dermatitis in vivo. (2014)
  • Author(s): Bando K, Takahashi H, Kinbara M, Tanaka Y, Kuroishi T, Sasaki K, Takano-Yamamoto T, Sugawara S, Endo Y.
  • Journal Title: journal of dental research Volume: 93 Issue: 11 Pages: 1101-1107
  • DOI: 10.1177/0022034514552674
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Roles played by histamine in strenuous or prolonged masseter muscle activity in mice. (2013)
  • Author(s): Yoneda H, Niijima-Yaoita F, Tsuchiya M, Kumamoto H, Watanabe M, Ohtsu H, Yanai K, Tadano T, Sasaki K, Sugawara S, Endo Y.
  • Journal Title: Clin Exp Pharmacol Physiol. Volume: 40 Issue: 12 Pages: 848-855
  • DOI: 10.1111/1440-1681.12167
  • Peer Reviewed
• [Journal Article] Influence of a long-term powdered diet on the social interaction test and dopaminergic systems in mice. (2013)
  • Author(s): Niijima-Yaoita F, Tsuchiya M, Saito H, Nagasawa Y, Murai S, Arai Y, Nakagawasai O, Nemoto W, Tadano T, Tan-No K.
  • Journal Title: Neurochem Int. Volume: 63 Issue: 4 Pages: 309-315
  • DOI: 10.1016/j.neuint.2013.07.004
  • Peer Reviewed
• [Journal Article] Extracellular ATP inhibits IL-1-induced MMP-1 expression through the action of CD39/nucleotidase triphosphate dephosphorylase-1 on human gingival fibroblasts. (2013)
  • Author(s): Nemoto E, Gotoh K, Tsuchiya M, Sakisaka Y, Shimauchi H.
  • Journal Title: Int Immunopharmacol. Volume: 17 Issue: 3 Pages: 513-518
  • DOI: 10.1016/j.intimp.2013.07.014
  • Peer Reviewed
• [Journal Article] Physiological distal drift in rat molars contributes to acellular cementum formation. (2013)
  • Author(s): Tsuchiya S, Tsuchiya M, Nishioka T, Suzuki O, Sasano Y, Igarashi K.
  • Journal Title: Anat Rec. Volume: 296 Issue: 8 Pages: 1255-1263
  • DOI: 10.1002/ar.22731
  • Peer Reviewed
• [Journal Article] Prompt analgesic effect of antihistaminic diphenhydramine ointment on bone-joint-muscle pain as assessed by skin impedance. (2013)
  • Author(s): Fujita T, Ohue M, Fujii Y, Jotoku T, Miyauchi A, Takagi Y, Tsuchiya M, Endo Y.
  • Journal Title: Pharmacology. Volume: 92 Issue: 3-4 Pages: 158-166
  • DOI: 10.1159/000354151
  • Peer Reviewed
• [Journal Article] Nanohydroxyapatite increases BMP-2 expression via a p38 MAP kinase dependent pathway in periodontal ligament cells (2013)
  • Author(s): Suto M, Nemoto E, Kanaya S, Suzuki R, Tsuchiya M, Shimauchi H
  • Journal Title: Arch Oral Biol Volume: 58巻 Issue: 8 Pages: 1021-1028
  • DOI: 10.1016/j.archoralbio.2013.02.014
  • Peer Reviewed
• [Journal Article] Joint immobilization induced hypoxic and inflammatory conditions in rat knee joints. (2013)
  • Author(s): Yabe Y, Hagiwara Y, Suda H, Ando A, Onoda Y, Tsuchiya M, Hatori K, Itoi E.
  • Journal Title: Connect Tissue Res. Volume: 54 Issue: 3 Pages: 210-217
  • DOI: 10.3109/03008207.2013.786056
  • Peer Reviewed
• [Journal Article] Joint Immobilization Indused Hypoxic and Inflammatory Conditions in Rat Knee Joints. (2013)
  • Author(s): Yabe Y, Hagiwara Y, Suda H, Ando A, Onoda Y, Tsuchiya M, Hatori K, Itoi E.
  • Journal Title: Connect Tissue Res. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Interleukin-6 Maintains Glucose Homeostasis to Support Strenuous Masseter Muscle Activity in Mice (2012)
  • Author(s): Tsuchiya M
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 227 Issue: 2 Pages: 109-117
  • DOI: 10.1620/tjem.227.109
  • NAID: 130004459984
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] Wnt5a signaling is a substantial constituent in bone morphogenetic protein-2-mediated osteoblastogenesis (2012)
  • Author(s): Nemoto E, Ebe Y, Kanaya S, Tsuchiya M, Nakamura T, Tamura M, Shimauchi H
  • Journal Title: Biochem Biophys Res Commun Volume: 422(4) Issue: 4 Pages: 627-632
  • DOI: 10.1016/j.bbrc.2012.05.039
  • Peer Reviewed
• [Presentation] Association of verbal abuse and physical violence from coaches with joint and limb pains of children engaged in junior club sports activity: a cross-sectional study. (2016)
  • Author(s): Kuroki K, Hagiwara Y, Yabe Y, Kanazawa K, Koide M, Itaya N, Sekiguchi T, Tsuchiya M, Momma H, Nagatomi R
  • Organizer: The 35th SITEMSH Congress.
  • Place of Presentation: Fukushima
  • Year and Date: 2016-03-13
  • Int'l Joint Research
• [Presentation] The Human Satellite Cells can Form the Myotube Even in the Atrophic Fatty Muscle of Rotator Cuff Tear. (2016)
  • Author(s): Koide M, Hagiwara Y, Ando A, Yabe Y, Kanazawa K, Sekiguchi T, Itaya N, Yoshida S, Itoi E, Kanzaki M, Hatakeyama H, Tsuchiya M.
  • Organizer: ORS 2016 Annual Meeting
  • Place of Presentation: Orlando
  • Year and Date: 2016-03-05
  • Int'l Joint Research
• [Presentation] Decreased Elastic Fibers and Increased Proteoglycans in the Ligamentum Flavum of Patients with Lumbar Spinal Canal Stenosis. (2016)
  • Author(s): Yabe Y, Hagiwara Y, Tsuchiya M, Honda M, Hatori K, Sonofuchi K, Kanazawa K, Koide M, Sekiguchi T, Itaya N, Itoi E.
  • Organizer: ORS 2016 Annual Meeting
  • Place of Presentation: Orlando
  • Year and Date: 2016-03-05
  • Int'l Joint Research
• [Presentation] Wnt3a signaling induces murine dental follicle cells to differentiate into cementoblastic/osteoblastic cells via an osterix-dependent pathway. (2016)
  • Author(s): Nemoto E, Sakisaka Y, Tsuchiya M, Tamura M, Nakamura T, Kanaya S, Shimauchi H.
  • Organizer: The 6th International Symposium for Interface Oral Health Science.
  • Place of Presentation: Sendai
  • Year and Date: 2016-01-18
  • Int'l Joint Research
• [Presentation] 学童期のスポーツ活動における慢性的な痛みと指導方法の関連：横断研究． (2015)
  • Author(s): 黒木薫、萩原嘉廣、矢部裕、金澤憲治、小出将志、板谷信行、関口拓矢、土谷昌広、永富良一．
  • Organizer: 第26回日本臨床スポーツ医学会学術集会．
  • Place of Presentation: 神戸
  • Year and Date: 2015-11-07
• [Presentation] 学童期におけるスポーツ活動中の怪我の経験と指導方法の関連：横断研究． (2015)
  • Author(s): 黒木薫、萩原嘉廣、矢部裕、金澤憲治、小出将志、板谷信行、関口拓矢、土谷昌広、門間陽樹、永富良一．
  • Organizer: 第18回日本運動疫学会学術総会．
  • Place of Presentation: 名古屋
  • Year and Date: 2015-06-20
• [Presentation] 第一世代抗ヒスタミン薬の鎮痛効果 (2014)
  • Author(s): 高橋萌、島和弘、土谷昌広、渡邉誠、菅原俊二、遠藤康男
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-27
• [Presentation] N-BPsはalkyl 型・heterocyclic 型を問わずリン酸トランスポーター SLC20/34 を介して細胞内に取り込まれ炎症壊死を起こす (2014)
  • Author(s): 佐藤衣莉,、土谷昌広、木山朋美、大泉丈史、山口晃史、菅原俊二、遠藤康男
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-26
• [Presentation] 窒素含有 bisphosphonates（N-BPs）治療患者での顎骨壊死：N-BPs の etidronate（non-N-BP）への置換の試み (2014)
  • Author(s): 大泉 丈史、山口晃史、鈴木飛佳理、土谷昌広、菅原俊二、高橋哲、遠藤康男
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-26
• [Presentation] 粉末食長期飼育はマウス糖代謝機構を障害し社会性行動の変化をもたらす (2014)
  • Author(s): 千葉航、土谷昌広、渡邉誠、菅原俊二、遠藤康男
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-26
• [Presentation] 長期飼育における粉末食のマウス糖代謝機構への影響と行動異常の誘発に関する研究 (2014)
  • Author(s): 千葉 航，土谷昌広，渡邉 誠，佐々木啓一，坪井明人，服部佳功
  • Organizer: 日本補綴歯科学会第123回学術大会
  • Place of Presentation: 仙台
  • Year and Date: 2014-05-25
• [Presentation] Roles played by IL-1 in prolonged masseter muscle activity in mice (2014)
  • Author(s): Chiba K, Tsuchiya M, Sasaki K, Tsuboi A, Hattori Y, Sugawara S, Endo Y
  • Organizer: The 5th international symposium for interface oral health symposium
  • Place of Presentation: Sendai
• [Presentation] マウス咬筋長時間活動におけるヒスタミンの役割 (2013)
  • Author(s): 米田博行，土谷昌広，八百板(新島)富紀枝，佐々木啓一，渡邉 誠，菅原俊二， 遠藤康男
  • Organizer: 日本顎口腔機能学会 第50回記念学術大会
  • Place of Presentation: 東京
• [Presentation] 粉末食飼育はマウスの糖代謝機構を障害し,行動異常を誘発する (2013)
  • Author(s): 千葉航，土谷昌広，八百板(新島)富紀枝，米田博行，渡邉誠，佐々木啓一
  • Organizer: 日本老年歯科医学会 第24回 学術大会
  • Place of Presentation: 大阪
• [Presentation] マウス咬筋の持続的活動におけるIL-1の役割 (2012)
  • Author(s): 千葉航,土谷昌広,米田博行,菅原俊二,遠藤康男
  • Organizer: 第54回歯科基礎医学会学術大会・総会
  • Place of Presentation: 郡山
  • Year and Date: 2012-09-14
• [Presentation] IL-6はマウス咬筋の激しい活動におけるグルコース維持に関与する. (2012)
  • Author(s): 木山朋美,土谷昌広,佐々木啓一,菅原俊二,遠藤康男
  • Organizer: 第54回歯科基礎医学会学術大会・総会
  • Place of Presentation: 郡山
  • Year and Date: 2012-09-14
• [Presentation] Pathogenesis of capsules in idiopathic frozen shoulders (2012)
  • Author(s): Hagiwara Y, Ando A, Onoda Y, Takemura T, Minowa T, Hanagata N, Tsuchiya M, Chimoto E, Suda H, Takahashi N, Sugaya H, Saijo Y, Itoi E
  • Organizer: 13th EFORT Congress 2012
  • Place of Presentation: Berlin
  • Year and Date: 2012-05-24
• [Presentation] 断続的断眠ストレス負荷誘発性交替行動障害に対するメチルフェニデートの改善作用について. (2012)
  • Author(s): 八百坂富紀枝,永澤佑佳,土谷昌広,仲川西修,根本亙,荒井裕一朗,只野武,丹野孝一
  • Organizer: 平成24年度東北薬科大学創薬研究センターシンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2012-05-19
• [Presentation] 粉末食飼育マウスにおけるSocial interactionの障害について
  • Author(s): 八百板富紀枝，荒井香，下道麻夏，齊藤貴之，土谷昌広，斉藤弘子，村井繁夫，荒井裕一朗，根本亙，中川西修，只野武，丹野孝一
  • Organizer: 平成25年度東北薬科大学創薬研究センターシンポジウム
  • Place of Presentation: 仙台
• [Presentation] 骨粗鬆症・変形性関節症でのジフェンヒドラミン軟膏の鎮痛作用：skin impedance による評価
  • Author(s): 藤田拓男，大植睦，藤井芳夫，常徳剛，宮内章光，高木康行，土谷昌広，遠藤康男
  • Organizer: 第17回日本ヒスタミン学会
  • Place of Presentation: 松江