Molecular mechanisms of cartilage degeneration by mechanical stress

2008 Fiscal Year Final Research Report

• Project/Area Number: 18390407
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: HOSHI Kazuto The University of Tokyo, 医学部・附属病院, 特任准教授 (30344451)
• Co-Investigator(Renkei-kenkyūsha): HOSHI Kazuto 東京大学, 医学部・附属病院, 特任准教授 (30344451) ; OGATA Naoshi 東京大学, 医学部・附属病院, 特任助教 (10361495) ; HARA Yoshihiro 東京大学, 医学部・附属病院, 助教 (00422296) ; HARA Yukinori 東京大学, 医学部・附属病院, 医員 (30396741)
• Project Period (FY): 2006 – 2008
• Keywords: 関節軟骨 / 力学的負荷 / 軟骨細胞 / 遺伝子改変マウス / Runx2 / Sox9

Research Abstract

メカニカルストレスは変形性関節症をはじめ、骨粗鬆症、骨折治癒など、整形外科における多くの病態で中心的な役割を果たす重要な因子と考えられている。しかし、その分子メカニズムについては殆ど解明されていない。本研究では、メカニカルストレスによる関節軟骨変性の分子機構を解明することを目的とし、軟骨において肥大分化促進因子として働くRunx2(Runt relatedtranscription factor 2)シグナルや軟骨初期分化に必須のSox9(SRY-box containing gene 9)シグナルなどに着眼し、各種遺伝子欠損マウスにおける膝関節不安定性モデル(メカニカルストレス過剰負荷モデル)実験モデルの解析を行い、関節軟骨変性に関連する分子シグナルの詳細を明らかにした。

Research Products

• [Journal Article] An animal model study for tissue-engineered trachea fabricated from a biodegradable scaffold using chondrocytes to augment repair of tracheal stenosis (2008)
  • Author(s): Komura M, Komura H, Kanamori Y, Tanaka Y, Suzuki K, Sugiyama M, Nakahara S, Kawashima H, Hatanaka A, Hoshi K, Ikada Y, Tabata Y, Iwanaka T
  • Journal Title: J Pediatr Surg 43(12) Pages: 2141-6
  • Peer Reviewed
• [Journal Article] Aptitude of auricular and nasoseptal chondrocytes cultured under a monolayer or three-dimensional condition for cartilage tissue engineering (2008)
  • Author(s): Asawa Y, Ogasawara T, Takahashi T, Yamaoka H, Nishizawa S, Matsudaira K, Mori Y, Takato T, Hoshi K
  • Journal Title: Tissue Eng Part A
  • Peer Reviewed
• [Journal Article] Growth factor contents of autologous human sera prepared by different production methods and their biological effects on chondrocytes (2008)
  • Author(s): Tanaka Y, Ogasawara T, Asawa Y, Yamaoka H, Nishizawa S, Mori Y, Takato T, Hoshi K
  • Journal Title: Cell Biol Int 32(5) Pages: 505-14
  • Peer Reviewed
• [Journal Article] Human tracheal chondrocytes as a cell source for augmenting stenotic tracheal segments : the first feasibility study in an in vivo culture system (2008)
  • Author(s): Komura M, Komura H, Tanaka Y, Kanamori Y, Sugiyama M, Nakahara S, Kawashima H, Suzuki K, Hoshi K, Iwanaka T
  • Journal Title: Pediatr Surg Int 24(10) Pages: 1117-21
  • Peer Reviewed
• [Journal Article] Kruppel-like factor 5 causes cartilage degradation through transactivation of matrix metalloproteinase 9 (2008)
  • Author(s): Shinoda Y, Ogata N, Higashikawa A, Manabe I, Shindo T, Yamada T, Kugimiya F, Ikeda T, Kawamura N, Kawasaki Y, Tsushima K, Takeda N, Nagai R, Hoshi K, Nakamura K, Chung UI, Kawaguchi H
  • Journal Title: J Biol Chem 283(36) Pages: 24682-9
  • Peer Reviewed
• [Journal Article] Phosphorylation of GSK-3beta by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes (2008)
  • Author(s): Kawasaki Y, Kugimiya F, Chikuda H, Kamekura S, Ikeda T, Kawamura N, Saito T, Shinoda Y, Higashikawa A, Yano F, Ogasawara T, Ogata N, Hoshi K, Hofmann F, Woodgett JR, Nakamura K, Chung UI, Kawaguchi H
  • Journal Title: J Clin Invest 118(7) Pages: 2506-15
  • Peer Reviewed
• [Journal Article] Akt1 in osteoblasts and osteoclasts controls bone remodeling (2007)
  • Author(s): Kawamura N, Kugimiya F, Oshima Y, Ohba S, Ikeda T, Saito T, Shinoda Y, Kawasaki Y, Ogata N, Hoshi K, Akiyama T, Chen WS, Hay N, Tobe K, Kadowaki T, Azuma Y, Tanaka S, Nakamura K, Chung UI, Kawaguchi H
  • Journal Title: PLoS ONE 2(10) Pages: e1058
  • Peer Reviewed
• [Journal Article] Erk pathways negatively regulate matrix mineralization (2007)
  • Author(s): Kono SJ, Oshima Y, Hoshi K, Bonewald LF, Oda H, Nakamura K, Kawaguchi H, Tanaka S
  • Journal Title: Bone 40(1) Pages: 68-74
  • Peer Reviewed
• [Journal Article] Hard tissue formation in subcutaneously transplanted rat dental pulp (2007)
  • Author(s): Hosoya A, Nakamura H, Ninomiya T, Hoshi K, Yoshiba K, Yoshiba N, Takahashi M, Okabe T, Sahara N, Yamada H, Kasahara E, Ozawa H
  • Journal Title: J Dent Res 86(5) Pages: 469-74
  • Peer Reviewed
• [Journal Article] Optimal combination of soluble factors for tissue engineering of permanent cartilage from cultured human chondrocytes (2007)
  • Author(s): Liu G, Kawaguchi H, Ogasawara T, Asawa Y, Kishimoto J, Takahashi T, Chung UI, Yamaoka H, Asato H, Nakamura K, Takato T, Hoshi K
  • Journal Title: J Biol Chem 282(28) Pages: 20407-15
  • Peer Reviewed
• [Journal Article] Three-dimensional microenvironments retain chondrocyte phenotypes during proliferation culture (2007)
  • Author(s): Takahashi T, Ogasawara T, Asawa Y, Mori Y, Uchinuma E, Takato T, Hoshi K
  • Journal Title: Tissue Eng 13(7) Pages: 1583-92
  • Peer Reviewed
• [Journal Article] Continuous activation of G alpha q in osteoblasts results in osteopenia through impaired osteoblast differentiation (2007)
  • Author(s): Ogata N, Kawaguchi H, Chung UI, Roth SI, Segre GV
  • Journal Title: J Biol Chem 2007 282(49) Pages: 35757-64
  • Peer Reviewed
• [Journal Article] Suppression of adjuvant-induced arthritic bone destruction by cyclooxygenase-2 selective agents with and without inhibitory potency against carbonic anhydrase II (2006)
  • Author(s): 14. Katagiri M, Ogasawara T, Hoshi K, Chikazu D, Kimoto A, Noguchi M, Sasamata M, Harada S, Akama H, Tazaki H, Chung UI, Takato T, Nakamura K, Kawaguchi H
  • Journal Title: J Bone Miner Res 21 Pages: 219-27
  • Peer Reviewed
• [Journal Article] Physiological role of bone morphogenetic proteins in osteogenesis (2006)
  • Author(s): Kugimiya F, Ohba S, Nakamura K, Kawaguchi H, Chung UI
  • Journal Title: J Bone Miner Metab 24 Pages: 95-9
  • Peer Reviewed
• [Journal Article] Risk factors for knee osteoarthritis in Japanese men : a case-control study (2006)
  • Author(s): Yoshimura N, Kinoshita H, Hori N, Nishioka T, Ryujin M, Mantani Y, Miyake M, Takeshita T, Ichinose M, Yoshida M, Oka H, Kawaguchi H, Nakamura K, Cooper C
  • Journal Title: Mod Rheumatol 16 Pages: 24-9
  • Peer Reviewed
• [Journal Article] Neurological level diagnosis of cervical stenotic myelopathy (2006)
  • Author(s): Seichi A, Takeshita K, Kawaguchi H, Matsudaira K, Higashikawa A, Ogata N, Nakamura K
  • Journal Title: Spine 31 Pages: 1338-43
  • Peer Reviewed
• [Journal Article] Vertebral hemangioma compressing the thoracic spinal cord : application of computer-aided navigation and intraoperative spinal sonography for surgery through anterior and posterior approaches (2006)
  • Author(s): Sakanishi H, Hoshi K, Nakajima S, Akune T, Takeshita K, Yamamoto M, Kawaguchi H, Nakamura K, Seichi A
  • Journal Title: J Orthop Sci 11 Pages: 294-7
  • Peer Reviewed
• [Journal Article] Carminerin contributes to chondrocyte calcification during endochondral ossification (2006)
  • Author(s): Yamada T, Kawano H, Koshizuka Y, Fukuda T, Yoshimura K, Kamekura S, Saito T, Ikeda T, Kawasaki Y, Azuma Y, Ikegawa S, Hoshi K, Chung UI, Nakamura K, Kato S, Kawaguchi H
  • Journal Title: Nature Med 12 Pages: 665-670
• [Journal Article] Cartilage tissue engineering using human auricular chondrocytes embedded in different hydrogel materials (2006)
  • Author(s): Yamaoka H, Asato H, Ogasawara T, Nishizawa S, Takahashi T, Nakatsuka T, Koshima I, Nakamura K, Kawaguchi H, Chung UI, Takato T, Hoshi K
  • Journal Title: J Biomed Mater Res A 78 Pages: 1-11
  • Peer Reviewed
• [Journal Article] A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine (2006)
  • Author(s): Horikoshi T, Maeda K, Kawaguchi Y, Chiba K, Mori K, Koshizuka Y, Hirabayashi S, Sugimori K, Matsumoto M, Kawaguchi H, Takahashi M, Inoue H, Kimura T, Matsusue Y, Inoue I, Baba H, Nakamura K, Ikegawa S
  • Journal Title: Hum Genet 119 Pages: 611-6
  • Peer Reviewed
• [Journal Article] Decreased activities of daily living and associations with bone loss among aged residents in a rural Japanese community : the Miyama Study (2006)
  • Author(s): Oka H, Yoshimura N, Kinoshita H, Saiga A, Kawaguchi H, Nakamura K
  • Journal Title: J Bone Miner Metab 24 Pages: 307-13
  • Peer Reviewed
• [Journal Article] Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability. Runx2 contributes to pathogenesis of osteoarthritis in mice after induction of knee joint instability (2006)
  • Author(s): Kamekura S, Kawasaki Y, Hoshi K, Shimoaka T, Chikuda H, Maruyama Z, Komori T, Sato S, Takeda S, Karsenty G, Nakamura K, Chung UI, Kawaguchi H
  • Journal Title: Arthritis Rheum 54 Pages: 2462-70
  • Peer Reviewed
• [Journal Article] Cumulative incidence and changes in prevalence of vertebral fractures in a rural Japanese community : A 10-year follow-up of the Miyama cohort (2006)
  • Author(s): Yoshimura N, Kinoshita H, Oka H, Muraki S, Mabuchi A, Kawaguchi H, Nakamura K
  • Journal Title: Arch Osteoporosis DOI10.1007/s11657-006-0007-0(online publication)
  • Peer Reviewed
• [Journal Article] Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways (2006)
  • Author(s): Shinoda Y, Yamaguchi M, Ogata N, Akune T, Kubota N, Yamauchi T, Terauchi Y, Kadowaki T, Takeuchi Y, Fukumoto S, Ikeda T, Hoshi K, Chung UI, Nakamura K, Kawaguchi H
  • Journal Title: J Cell Biochem 99 Pages: 196-208
  • Peer Reviewed
• [Journal Article] Distinct association of gene polymorphisms of estrogen receptor and vitamin D receptor with lumbar spondylosis in postmenopausal women (2006)
  • Author(s): Koshizuka Y, Ogata N, Shiraki M, Hosoi T, Seichi A, Takeshita K, Nakamura K, Kawaguchi H
  • Journal Title: Eur Spine J 15 Pages: 1521-1528
• [Journal Article] Tailor-made tricalcium phosphate bone implant directly fabricated by a three-dimensional ink-jet printer (2006)
  • Author(s): Igawa K, Mochizuki M, Sugimori O, Shimizu K, Yamazawa Y, Kawaguchi H, Nakamura K, Takato T, Nishimura R, Suzuki S, Anzai M, Chung UI, Sasaki N
  • Journal Title: J Artif Organs 9 Pages: 234-40
  • Peer Reviewed
• [Journal Article] Tissue reactions to engineered cartilage based on poly-L-lactic acid scaffolds
  • Author(s): Fujihara Y, Asawa Y, Takato T, Hoshi K
  • Journal Title: Tissue Eng Part A
  • Peer Reviewed
• [Journal Article] Grafting of biocompatible polymer for longevity of artificial hip joints
  • Author(s): Moro T, Takatori Y, Ishihara K, Nakamura K and Kawaguchi H
  • Journal Title: Clin Orthop Rel Res 453 Pages: 58-63
  • Peer Reviewed
• [Presentation] 糖代謝・脂質代謝調節分子による骨代謝制御 : マウスジェネティクスからのアプローチ : シンポジウム6 (2007)
  • Author(s): 川口浩、阿久根徹、緒方直史、星和人、篠田裕介、河村直洋、山口雅之、鄭雄一、門脇孝、中村耕三
  • Organizer: 骨粗鬆症と骨関節疾患の遺伝学 : 第9回日本骨粗鬆症学会
  • Place of Presentation: 東京都新宿区
  • Year and Date: 2007-11-16
• [Presentation] 関節軟骨再生の現状と展望 : シンポジウム3 (2007)
  • Author(s): 星和人、川口浩、鄭雄一、高戸毅、中村耕三
  • Organizer: 骨関節老化の基礎と臨床 : 第9回日本骨粗鬆症学会
  • Place of Presentation: 東京都新宿区
  • Year and Date: 2007-11-14
• [Presentation] 糖代謝と骨代謝に関連するAktシグナル (2007)
  • Author(s): 川口浩、河村直洋、緒方直史、阿久根徹、山口雅之、星和人、門脇孝、中村耕三
  • Organizer: 生活習慣と骨代謝 : 第25回日本骨代謝学会学術集会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2007-07-19
• [Presentation] 永久軟骨を再生させるための軟骨細胞増殖・基質産生培養法の開発とその作用機序 : ワークショップ11 (2007)
  • Author(s): 星和人、中村耕三、川口浩
  • Organizer: 軟骨の変性と再生機序 : 第51回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2007-04-29
• [Presentation] 永久軟骨を再生させるための軟骨細胞再分化誘導法の検討と作用機序の解明 (2006)
  • Author(s): 星和人、鄭雄一、中村耕三、川口浩
  • Organizer: 第21回日本整形外科学会基礎学術集会
  • Place of Presentation: 長崎県長崎市
  • Year and Date: 20061019-20
• [Presentation] Optimal Combination of Soluble Factors for Tissue Engineering of Permanent Cartilage with High Quality and Quantity from Autologous Human Chondrocytes (2006)
  • Author(s): Hoshi K, Liu G, Ogasawara T, Asawa Y, Takahashi T, Yamaoka U, Chung UI, Takato T, Nakamura K, Kawaguchi H
  • Organizer: ASBMR 28^<th> Annual Meeting
  • Place of Presentation: Philadelphia, Pennsylvania, USA
  • Year and Date: 20060915-19
• [Presentation] 糖代謝、脂質代謝調節分子による骨代謝制御 (2006)
  • Author(s): 川口浩、阿久根徹、緒方直史、星和人、篠田裕介、河村直洋、山口雅之、鄭雄一、門脇孝、中村耕三
  • Organizer: 第24回日本骨代謝学会学術集会
  • Place of Presentation: 東京都江東区
  • Year and Date: 20060706-08
• [Presentation] 自家軟骨細胞から大量永久軟骨再生のための最適シグナル条件の系統的・網羅的検索 (2006)
  • Author(s): 星和人、劉光耀、小笠原徹、浅輪幸世、高橋嗣明、鄭雄一、高戸毅、中村耕三、川口浩
  • Organizer: 第24回日本骨代謝学会学術集会
  • Place of Presentation: 東京都江東区
  • Year and Date: 20060706-08
• [Book] 症候6四肢の症候小項目6「背部痛」(永井良三(編)) (2008)
  • Author(s): 星和人, 原慶宏, 森井太郎, 松平浩
  • Total Pages: 1491-1492
  • Publisher: 看護に役立つ疾患・症候事典 メジカルフレンド 東京
• [Book] 第1章移植細胞の生物医学1)「成熟細胞軟骨細胞」(田畑泰彦(編)) (2008)
  • Author(s): 星和人, 高戸毅
  • Total Pages: 32-37
  • Publisher: 進みつづける細胞移植治療の実際 メディカルドゥ 大阪
• [Book] Experimental Murine Model of Ossfication of Spinal Ligements Induced by Bone Morphogenetic Protein-(Yonenobu K, Nakamura K, Toyama Y(eds)) (2006)
  • Author(s): Hoshi K
  • Total Pages: 93-100
  • Publisher: Ossification of the Posterior Longitudinal Ligament 2nd Edition, Springer, Tokyo
• [Book] 第6章「骨」(加藤隆史(編)) (2006)
  • Author(s): 星和人
  • Total Pages: 75-87
  • Publisher: バイオミネラリゼーションとそれに倣う新機能材料の創製シーエムシー出版 東京