Centers & Labs

RIKEN Center for Integrative Medical Sciences

Laboratory for Bone and Joint Diseases

Team Leader: Shiro Ikegawa (M.D., Ph.D)
Shiro  Ikegawa(M.D., Ph.D)

We are studying genetic factors of the locomotive system, in particular, of bone and joint. The main feature of our lab is to study monogenic and polygenic diseases simultaneously and comprehensively by starting from human diseases. There are many intractable diseases in the monogenic diseases of the locomotive system, including skeletal dysplasia. We have discovered 17 disease genes so far. The polygenic diseases of the locomotive system include osteoarthritis osteoporosis and disc degeneration. We are tackling on development of innovative methods of diagnosis and treatment of the diseases based on identification of their susceptibility genes. Through the analysis of the genes, we are trying to clarify the mechanism of growth and development of the locomotive system.

Main Research Field

Medicine, dentistry, and pharmacy

Related Research Fields

Biological Sciences

Research Subjects

  • Genome analysis of monogenic diseases of the locomotive system (bone and joint) including skeletal dysplasias and connective tissue diseases
  • Genome analysis of polygenic diseases of the locomotive system including skeletal osteoarthritis, disc herniation, OPLL, osteoporosis, osteonecrosis of the femoral head, and scoliosis
  • Mechanism of formation, groth and development of human skeleton
  • Regenerative medicine

Selected Publications

Papers with an asterisk(*) are based on research conducted outside of RIKEN.
  1. Nakajima M, Takahashi A, Tsuji T, Karasugi T, Baba H, Uchida K, Kawabata S, Okawa A, Shindo S, Takeuchi K, Taniguchi Y, Maeda S, Kashii M, Seichi A, Nakajima H, Kawaguchi Y, Fujibayashi S, Takahata M, Tanaka T, Watanabe K, Kida K, Kanchiku T, Ito Z, Mori K, Kaito T, Kobayashi S, Yamada K, Takahashi M, Chiba K, Matsumoto M, Furukawa KI, Kubo M, Toyama Y;Genetic Study Group of Investigation Committee on Ossification of the Spinal Ligaments, Ikegawa S.:
    "A genome-wide association study identifies susceptibility loci for ossification of the posterior longitudinal ligament of the spine."
    Nat Genet 46(9):1012-6, 2014.
  2. Kou I, Takahashi Y, Johnson TA, Takahashi A, Guo L, Dai J, Qiu X, Sharma S, Takimoto A, Ogura Y, Jiang H, Yan H, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Hosono N, Tsuji T, Suzuki T, Sudo H, Kotani T, Yonezawa I, Londono D, Gordon D, Herring JA, Watanabe K, Chiba K, Kamatani N, Jiang Q, Hiraki Y, Kubo M, Toyama Y, Tsunoda T, Wise CA, Qiu Y, Shukunami C, Matsumoto M, and Ikegawa S.:
    "Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis."
    Nat Genet 45(6), 676-9 (2013)
  3. Takahashi Y, Kou I, Takahashi A, Johnson TA, Kono K, Kawakami N, Uno K, Ito M, Minami S, Yanagida H, Taneichi H, Tsuji T, Suzuki T, Sudo H, Kotani T, Watanabe K, Chiba K, Hosono N, Kamatani N, Tsunoda T, Toyama Y, Kubo M, Matsumoto M, and Ikegawa S.:
    "A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis."
    Nat Genet 43(12), 1237-40 (2011)
  4. Miyamoto Y, Shi D, Nakajima M, Ozaki K, Sudo A, Kotani A, Uchida A, Tanaka T, Fukui N, Tsunoda T, Takahashi A, Nakamura Y, Jiang Q, and Ikegawa S.:
    "Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis."
    Nat Genet 40(8), 994-8 (2008)
  5. Hiraoka S, Furuichi T, Nishimura G, Shibata S, Yanagishita M, Rimoin DL, Superti-Furga A, Nikkels PG, Ogawa M, Katsuyama K, Toyoda H, Kinoshita-Toyoda A, Ishida N, Isono K, Sanai Y, Cohn DH, Koseki H, and Ikegawa S.:
    "Nucleotide-sugar transporter SLC35D1 is critical to chondroitin sulfate synthesis in cartilage and skeletal development in mouse and human."
    Nat Med 13(11), 1363-7 (2007)
  6. Miyamoto Y, Mabuchi A, Shi D, Kubo T, Takatori Y, Saito S, Fujioka M, Sudo A, Uchida A, Yamamoto S, Ozaki K, Takigawa M, Tanaka T, Nakamura Y, Jiang Q, and Ikegawa S.:
    "A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis."
    Nat Genet 39(4), 529-33 (2007)
  7. Seki S, Kawaguchi Y, Chiba K, Mikami Y, Kizawa H, Oya T, Mio F, Mori M, Miyamoto Y, Masuda I, Tsunoda T, Kamata M, Kubo T, Toyama Y, Kimura T, Nakamura Y, and Ikegawa S.:
    "A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease."
    Nat Genet 37(6), 607-12 (2005)
  8. Kizawa H, Kou I, Iida A, Sudo A, Miyamoto Y, Fukuda A, Mabuchi A, Kotani A, Kawakami A, Yamamoto S, Uchida N, Nakamura K, Notoya K, Nakamura Y, and Ikegawa S.:
    "An aspartic acid repeat polymorphism in asporin negatively affects chondrogenesis and increases susceptibility to osteoarthritis."
    Nat Genet 37(2), 138-44 (2005)
  9. *Okawa A, Nakamura I, Goto S, Moriya H, Nakamura Y, and Ikegawa S.:
    "Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine."
    Nat Genet 19(3), 271-31 (1998)

Lab Members

Principal Investigator

Shiro Ikegawa
Team Leader

Core Members

Aritoshi Iida
Senior Research Scientist
Ikuyo Inaba
Senior Research Scientist
Masahiro Nakajima
Research Scientist
Zheng Wang
Research Scientist
Long Guo
Postdoctoral Researcher
Yuma Sakamoto
Junior Research Associate
Yoshie Takahashi
Technical Staff II
Tomoko Kusadokoro
Technical Staff II
Tomomi Isono
Technical Staff II

Contact information

4-6-1 Shirokanedai,
Minato-ku, Tokyo
108-8639 JAPAN
Laboratory for Bone and Joint Diseases, SRC RIKEN.

Email: sikegawa [at] ims.u-tokyo.ac.jp

Related links

Recent research results

August 26, 2016: RIKEN RESEARCH
Sending bone growth down the spine
July 24, 2015: Press Release
The genetic roots of adolescent scoliosis