Osteogenic differentiation of culture expanded bone marrow cells under tensile and compressive strains

• Project/Area Number: 21591915
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya University
• Principal Investigator: KITOH Hiroshi 名古屋大学, 医学部附属病院, 講師 (40291174)
• Co-Investigator(Kenkyū-buntansha): KANEKO Hiroshi 名古屋大学, 大学院・医学系研究科, 講座助教 (60566975)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: メカニカルストレス / 骨髄細胞培養 / 骨組織再生 / 骨延長モデル / 多血小板血漿 / HIF 1α / 三次元培養 / 細胞培養 / 骨形成マーカー / 骨髄間葉系細胞 / 骨芽細胞分化 / VEGF

Research Abstract

Alkaline phosphatase activity within the culture media were significantly elevated in the dynamic stretch(DS) group and the dynamic compression(DC) group compared to the control group. The DC group showed significant elevated levels of mRNA expression of HIF 1α. Western blotting analysis demonstrated increased amount of HIF 1αprotein within the nucleous in the DC, DS, and static stretch(SS) groups. Favorable new bone formation was observed when the bone marrow cells cultured under the dynamic stretch condition were implanted with PRP into the distraction gap of rat bone lengthening models.

Research Products

• [Journal Article] Chondro blastoma of the femoral neck as a cause of hip synovitis (2012)
  • Author(s): Kaneko H, Kitoh H, Wasa J, Nishida Y, Ishiguro N.
  • Journal Title: J Pediatr O rthop(B) Volume: 21(2) Pages: 179-182
  • Peer Reviewed
• [Journal Article] Novel compound heterozygous mutations in the cathepsin K gene in Japanese female siblings with pyknodysostosis (2012)
  • Author(s): Matsushita M, Kitoh H, et al
  • Journal Title: Molecular Syndromology Volume: (未定)(In press)
  • Peer Reviewed
• [Journal Article] Spatial and temporal distribution of growth factors receptors in the callus : Implications for improve ment of distractio nosteo ge nesis (2011)
  • Author(s): Siwicka KA, Kitoh H, Kawasumi M, Ishiguro N.
  • Journal Title: Nagoya J Med Sci Volume: 73(3-4) Pages: 117-127
  • Peer Reviewed
• [Journal Article] Mutations in the TGFβbinding protein-like domain 5 of FBN1 are responsible acromicric and geleo physicdys plasias (2011)
  • Author(s): Le Goff C, Mahaut C, Wang LW, Allali S, Abhyankar A, Jensen S, Zilberberg L, Collod-Beroud G, Bonnet D, Alanay Y, Brady AF, Cordier MP, Devriendt K, Genevieve D, Kiper POS, Kitoh H, Krakow D, Lynch SA, Le Merrer M, Megarbane1A, Mortier G, Odent S, Polak M
  • Journal Title: Am J Hum Genet Volume: 89(1) Pages: 7-14
  • Peer Reviewed
• [Journal Article] Hy peruricemia cosegregating with osteo genesis imper fecta is associated with amutation in GPATCH8 (2011)
  • Author(s): Kaneko H, Kitoh H, Matsuura T, Masuda A, Ito M, Mottes M, Rauch F, Ishiguro N, Ohno K.
  • Journal Title: Hum Genet Volume: 130(5) Pages: 671-683
  • Peer Reviewed
• [Journal Article] Early clinical and radio graphic characte ristics in fibrody splasia ossifican sprogressiva : A report of two cases (2011)
  • Author(s): Mishima K, Kitoh H, Katagiri T, Kaneko H, Ishiguro N.
  • Journal Title: J Bone Joint Surg Volume: 93-A : e52 Pages: 1-5
  • Peer Reviewed
• [Journal Article] Factors related to surgical out come after posterior decompression and fusion for craniocervical junction lesions associated with osteogenesis imperfecta (2011)
  • Author(s): Imagama S, Wakao N, Kitoh H, Matsuyama Y, Ishiguro N.
  • Journal Title: Eur Spine J Suppl Volume: 2 : S Pages: 320-325
  • Peer Reviewed
• [Journal Article] A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H (2011)
  • Author(s): Ohte S, Shin M, Sasanuma H, Yoneyama K, Akita M, Ikebuchi K, Jimi E, Maruki Y, Matsuoka M, Miyazono K, Nanba A, Tomoda H, Okazaki Y, Ohtake A, Oda H, Owan I, Yoda T, Furuya H, Kamizono J, Kitoh H, Nakashima Y, Susami T, Haga N, Komori T, Katagiri T.
  • Journal Title: Biochem Biophys Res Commun Volume: 407(1) Pages: 213-8
  • Peer Reviewed
• [Journal Article] Spondylometaphyseal dysplasia with cone-rod dystrophy (2011)
  • Author(s): Kitoh H, Kaneko H, Kondo M, Yamamoto T, Ishiguro N, Nishimura G.
  • Journal Title: Am J Med Genet Volume: 155A Pages: 845-849
  • Peer Reviewed
• [Journal Article] 石黒直樹進行性骨化性線維異形成症における足部変形について (2011)
  • Author(s): 鬼頭浩史、西田佳弘、川澄本明
  • Journal Title: 東海足と靴の研究会誌 Volume: 4 Pages: 13-14
  • Peer Reviewed
• [Journal Article] 石黒直樹Ponseti法による先天性内反足の治療成績.全身性疾患や合併奇形の有無による成績の比較 (2011)
  • Author(s): 鬼頭浩史、北小路隆彦、金子浩史、馬渕晃好、三島健一
  • Journal Title: 日小整誌 Volume: 20(2) Pages: 353-356
  • Peer Reviewed
• [Journal Article] Spondylometaphyseal dysplasia with cone-rod dystrophy (2011)
  • Author(s): Kitoh H, Kaneko H, Kondo M, Yamamoto T, Ishiguro N, Nishimura G
  • Journal Title: Am J Med Genet A Volume: 155A(4) Issue: 4 Pages: 845-9
  • DOI: 10.1002/ajmg.a.33898
  • Peer Reviewed
• [Journal Article] A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H (2011)
  • Author(s): Ohte S, Kitoh H, et al
  • Journal Title: Biochemical Biophysical Research Communication Volume: 407 Pages: 213-218
  • Peer Reviewed
• [Journal Article] Factors related to surgical outcome after posterior decompression and fusion for craniocervical junction lesions associated with osteogenesis imperfecta (2011)
  • Author(s): Imagama S, Wakao N, Kitoh H, Matsuyama Y, Ishiguro N
  • Journal Title: Eur Spine J Volume: 20 Suppl 2 Issue: S2 Pages: 320-5
  • DOI: 10.1007/s00586-011-1734-5
  • Peer Reviewed
• [Journal Article] Early clinical and radiographic characteristics in fibrodysplasia ossificans progressiva : a report of two cases (2011)
  • Author(s): Mishima K, Kitoh H, Katagiri T, Kaneko H, Ishiguro N
  • Journal Title: J Bone Joint Surg Am Volume: 93(10) Issue: 10 Pages: e52(1)-e52(5)
  • DOI: 10.2106/jbjs.j.01443
  • Peer Reviewed
• [Journal Article] Hyperuricemia cosegregating with osteogenesis imperfecta is associated with a mutation in GPATCH8 (2011)
  • Author(s): Kaneko H, Kitoh H, Matsuura T, Masuda A, Ito M, Mottes M, Rauch F, Ishiguro N, Ohno K
  • Journal Title: Hum Genet Volume: 130 Issue: 5 Pages: 671-683
  • DOI: 10.1007/s00439-011-1006-9
  • Peer Reviewed
• [Journal Article] Mutations in the TGFβ binding protein-like domain 5 of FBN1 are responsible acromicric and geleophysic dysplasias (2011)
  • Author(s): Le Goff C, Kitoh H, et al
  • Journal Title: American Journal of Human Genetics Volume: 89 Issue: 1 Pages: 7-14
  • DOI: 10.1016/j.ajhg.2011.05.012
  • Peer Reviewed
• [Journal Article] Spatial and temporal distribution of growth factors receptors in the callus : Implications for improvement of distraction osteogenesis (2011)
  • Author(s): Siwicka KA, Kitoh H, et al
  • Journal Title: Nagoya Journal of Medical Science Volume: 73 Pages: 117-127
  • Peer Reviewed
• [Journal Article] Chondroblastoma of the femoral neck as a cause of hip synovitis (2011)
  • Author(s): Kaneko H, Kitoh H, et al
  • Journal Title: Journal of Pediatric Orthopaedics (B) Volume: 21 Pages: 179-182
  • Peer Reviewed
• [Journal Article] Spondylometaphyseal dysplasia with cone-rod dystrophy. (2011)
  • Author(s): Kitoh H, et. al.
  • Journal Title: American Journal of Medical Genetics(A) Volume: in press
  • Peer Reviewed
• [Journal Article] Early clinical and radiological characteristics in fibrodysplasia ossificans progressiva. (2011)
  • Author(s): Mishima K, Kitoh H, et. al.
  • Journal Title: Journal of Bone and Joint Surgery (Am) Volume: in press
  • Peer Reviewed
• [Journal Article] Deformity of the great toe in fibrodysplasia ossificans rogressive (2010)
  • Author(s): Nakashima Y, Haga N, Kitoh H, Kamizono J, Tozawa K, Katagiri T, Susami T, Fukushi J, Iwamoto Y.
  • Journal Title: J Orthop Sci Volume: 15(6) Pages: 804-809
  • Peer Reviewed
• [Journal Article] Novel and recurrentTRPV4 mutations and their association with distinct phenotypes within the TRPV4dysplasia family (2010)
  • Author(s): Dai J, Kim OH, Cho TJ, Schmidt-Rimpler M, Tonoki H, Takikawa K, Haga N, Miyoshi K, Kitoh H, Yoo WJ, Choi IH, Song HR, Jin DK, Kim HT, Kamasaki H, Bianchi P, Grigelioniene G, Nampoothiri S, Minagawa M, Miyagawa S, Fukao T, Marcelis C, Jansweijer MCE, Hennekam RCM, Bedeschi F, Mustonen A, Jiang Q, Ohashi H, Furuichi T, Unger S, Zabel B, Lausch E, Superti-Furga A, Nishimura N, Ikegawa S.
  • Journal Title: J Med Genet Volume: 47(10) Pages: 704-709
  • Peer Reviewed
• [Journal Article] Spondylo-epiphyseal dysplasia, Maroteaux type(pseudo-Morquio syndrome type 2) and parastremmatic dysplasia are caused byTRPV4 mutations (2010)
  • Author(s): Nishimura G, Dai J, Lausch E, Unger S, Megarbane A, Kitoh H, OH Kim, Cho TJ, Bedeschi F, Benedicenti F, Mendoza-Londono R, Silengo M, Schmidt-Rimpler M, Spranger J, Zabel B, kegawa S, Superti-Furga A.
  • Journal Title: Am J Med Genet Volume: 152A(6) Pages: 1443-1449
  • Peer Reviewed
• [Journal Article] Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2) and parastremmatic dysplasia are caused by TRPV4 mutations. (2010)
  • Author(s): Nishimura G, Kitoh H, et. al.
  • Journal Title: American Journal of Medical Genetics(A) Volume: 152 Pages: 1443-1449
  • Peer Reviewed
• [Journal Article] Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family. (2010)
  • Author(s): Dai J, Kitoh H, et. al.
  • Journal Title: Journal of Medical Genetics Volume: 47 Pages: 704-709
  • Peer Reviewed
• [Journal Article] Deformity of the great toe in fibrodysplasia ossificnas progressiva. (2010)
  • Author(s): Nakashima Y, Kitoh H, et. al.
  • Journal Title: Journal of Orthopaedic Science Volume: 15 Pages: 804-809
  • Peer Reviewed
• [Journal Article] Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family. (2010)
  • Author(s): Dai J, Kim OK, Cho TJ, Schmidt-Rimpler M, Tonoki H, Takikawa K, Haga N, Miyoshi K, Kitoh H, et. al
  • Journal Title: J Med Genet (in press)
  • Peer Reviewed
• [Journal Article] Induction of systemic bone changes by preconditioning total body irradiation for bone marrow transplantation (2009)
  • Author(s): Miyazaki O, Nishimura G, Okamoto R, Masaki H, Kumagai M, Shioda Y, Nozawa K, Kitoh H.
  • Journal Title: Pediatr Radiol Volume: 39 Pages: 23-29
  • Peer Reviewed
• [Journal Article] Predictive factors for unsuccessful treatment of developmental dysplasia of the hip by the Pavlik harness (2009)
  • Author(s): Kitoh H, Kawasumi M, Ishiguro N.
  • Journal Title: J Pediatr Orthop Volume: 29(6) Pages: 552-557
  • Peer Reviewed
• [Journal Article] Differential effects of culture expanded bone marrow cells transplantation on the regeneration of bone between the femora land the tibial lengthenings (2009)
  • Author(s): Kitoh H, Kawasumi M, Kaneko H, Ishiguro N.
  • Journal Title: J Pediatr Orthop Volume: 29(6) Pages: 643-649
  • Peer Reviewed
• [Journal Article] Radiographic analysis of movements of the acetabulum and the femoral head after Salter innominate osteotomy (2009)
  • Author(s): Kitoh H, Kaneko H, Ishiguro N.
  • Journal Title: J Pediatr Orthop Volume: 29(8) Pages: 879-884
  • Peer Reviewed
• [Journal Article] 小児疾患診療のための病態生理2筋・骨・運動器疾患軟骨無形成症 (2009)
  • Author(s): 鬼頭浩史
  • Journal Title: 小児内科 Volume: 41 Pages: 989-992
  • Peer Reviewed
• [Journal Article] Induction of systemic bone changes by preconditioning total body irradiation for bone marrow transplantation. (2009)
  • Author(s): Miyazaki O, Nishimura G, Okamoto R, Masaki H, Kumagai M, Shioda Y, Nozawa K, Kitoh H.
  • Journal Title: Pediatr Radiol 39 Pages: 23-29
  • Peer Reviewed
• [Journal Article] Predictive factors for unsuccessful treatment of developmental dysplasia of the hip by the Pavlik harness. (2009)
  • Author(s): Kitoh H, Kawasumi M, Ishiguro N.
  • Journal Title: J Pediatr Orthop 29(6) Pages: 552-557
  • Peer Reviewed
• [Journal Article] Differential effects of culture expanded bone marrow cells transplantation on the regeneration of bone between the femoral and the tibial lengthenings. (2009)
  • Author(s): Kitoh H, Kawasumi M, Kaneko H, Ishiguro N.
  • Journal Title: J Pediatr Orthop 29(6) Pages: 643-649
  • Peer Reviewed
• [Journal Article] Radiographic analysis of movements of the acetabulum and the femoral head after Salter innominate osteotomy. (2009)
  • Author(s): Kitoh H, Kaneko H, Ishiguro N.
  • Journal Title: J Pediatr Orthop 29(8) Pages: 879-884
  • Peer Reviewed
• [Presentation] Runx2のプロモーター活性を亢進し骨形成を促進する既存薬の検索 (2011)
  • Author(s): 三島健一、鬼頭浩史, 他
  • Organizer: 第26回日本整形外科学会基礎学術集会
  • Place of Presentation: 前橋市
  • Year and Date: 2011-10-21
• [Presentation] 軟骨無(低)形成症の身体的特徴 (2011)
  • Author(s): 鬼頭浩史、金子浩史、馬渕晃好、三島健一、石黒直樹
  • Organizer: 第26回東海小児整形外科懇話会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-02-19
• [Presentation] 重度大腿骨頭すべり症に対する創外固定法による骨切り術 (2011)
  • Author(s): 鬼頭浩史、金子浩史、馬渕晃好、三島健一、松下雅樹、石黒直樹、北小路隆彦、服部義
  • Organizer: 第22回日本小児整形外科学会
  • Place of Presentation: 京都
• [Presentation] ペルテス病の治療成績に関連する因子の検討 (2011)
  • Author(s): 鬼頭浩史、金子浩史、北小路隆彦、服部義、石黒直樹
  • Organizer: 第50回小児股関節研究会
  • Place of Presentation: 諏訪
• [Presentation] 進行性骨化性線維異形成症における早期(骨化発症前)の臨床的、X線学的特徴 (2011)
  • Author(s): 鬼頭浩史、三島健一、金子浩史、石黒直樹
  • Organizer: 第84回日本整形外科学会
  • Place of Presentation: 横浜
• [Presentation] Drug screening for transcriptional activation of SOX9 (2011)
  • Author(s): Hiroshi Kaneko, Hiroshi Kitoh, RyuichiroYamamoto, Naoki Ishiguro, Kinji Ohno
  • Organizer: 57th annual meeting of Orthopaedic Research Society
  • Place of Presentation: Long Beach
• [Presentation] Drug screening for transcriptional activation of Sox9 (2011)
  • Author(s): Kaneko H, Ktoh H, et al
  • Organizer: 57^<th> Annnual Meeting of Orthopaedic Research Society
  • Place of Presentation: Long Beach
• [Presentation] Ponseti法による先天性内反足の治療成績.全身性疾患や合併奇形の有無による成績の比較. (2010)
  • Author(s): 鬼頭浩史、金子浩史、北小路隆彦、石黒直樹
  • Organizer: 第21回日本小児整形外科学会
  • Place of Presentation: 徳島
• [Presentation] 骨系統疾患に対する培養骨髄細胞移植を併用した骨延長術 (2010)
  • Author(s): 鬼頭浩史、金子浩史、石黒直樹
  • Organizer: 第83回日本整形外科学会
  • Place of Presentation: 東京
• [Presentation] Phenotypic variability of osteogenesis imperfecta is not accounted for by disruption of splicing cis-elements (2010)
  • Author(s): Hiroshi Kaneko, Hiroshi Kitoh, Toru Matsuura, Akio Masuda, Ito Mikako, Monica Mottes, Frnk Rauch, Naoki Ishiguro, Kinji Ohno
  • Organizer: 56th annual meeting of Orthopaedic Research Society
  • Place of Presentation: New Orleans
• [Presentation] Limb leng thening and correction of deformities treated with culture expanded bone marrow cells and platelet rich plasma in skeletal dysplasias (2010)
  • Author(s): Hiroshi Kitoh, Hiroshi Kaneko, Naoki Ishiguro
  • Organizer: 56th annual meeting of Orthopaedic Research Society
  • Place of Presentation: New Orleans
• [Presentation] 骨系統疾患に対する培養骨髄細胞移植を併用した骨延長術 (2010)
  • Author(s): 鬼頭浩史, 他
  • Organizer: 日本整形外科学会
  • Place of Presentation: 東京フォーラム
• [Presentation] 進行性骨化性線維異形成症における骨化予防薬の検討 (2009)
  • Author(s): 鬼頭浩史、山本隆一郎、片桐岳信、大野欽司、石黒直樹
  • Organizer: 第21回日本整形外科学会骨系統疾患研究会
  • Place of Presentation: 松山
  • Year and Date: 2009-12-05
• [Presentation] 進行性骨化性線維異形成症における骨化予防薬の検討- (2009)
  • Author(s): 鬼頭浩史、山本隆一郎、井桐岳信、大野欽司、石黒直樹
  • Organizer: 第21回日本整形外科学会骨系統疾患研究会
  • Place of Presentation: 松山市
  • Year and Date: 2009-12-05
• [Presentation] ソルター骨盤骨切り術における臼蓋と大腿骨頭中心の移動について (2009)
  • Author(s): 鬼頭浩史、金子浩史、石黒直樹
  • Organizer: 第20回日本小児整形外科学会
  • Place of Presentation: 松山
• [Presentation] 培養骨髄細胞移植による仮骨形成促進効果の移植部位による相違-大腿骨延長と脛骨延長との比較- (2009)
  • Author(s): 鬼頭浩史、川澄本明、石黒直樹
  • Organizer: 第82回日本整形外科学会
  • Place of Presentation: 福岡
• [Presentation] 培養骨髄細胞移植による仮骨形成促進効果の移植部位による相違-大腿骨延長と脛骨延長との比較- (2009)
  • Author(s): 鬼頭浩史、川澄本明、石黒直樹
  • Organizer: 第82回日本整形外科学会
  • Place of Presentation: 福岡市
• [Presentation] ソルター骨盤骨切り術における臼蓋と大腿骨頭中心の移動について (2009)
  • Author(s): 鬼頭浩史、金子浩史、石黒直樹
  • Organizer: 第20回日本小児整形外科学会
  • Place of Presentation: 松山市
• [Book] 骨系統疾患児の治療と支援?整形外科からー骨系統疾患出生前診断と周産期管理 (2011)
  • Author(s): 鬼頭浩史
  • Publisher: メディカルビュー
• [Book] 弯曲骨異形成症 今日の整形外科治療指針 ６版 (2010)
  • Author(s): 鬼頭浩史
  • Publisher: 医学書院
• [Book] 遠位中間肢異形成症 今日の整形外科治療指針 ６版 (2010)
  • Author(s): 鬼頭浩史
  • Total Pages: 256
  • Publisher: 医学書院
• [Patent(Industrial Property Rights)] 骨形成促進剤及びその用途 (2011)
  • Inventor(s): 大野欽司、石黒直樹、鬼頭浩史、三島健一
  • Industrial Property Rights Holder: 名古屋大学
  • Filing Date: 2011-08-26
• [Patent(Industrial Property Rights)] 骨形成促進剤及びその用途 (2011)
  • Inventor(s): 大野欽司, 石黒直樹, 鬼頭浩史, 三島健一
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Number: 2011-185306
  • Filing Date: 2011-08-26