RIKEN Center for Integrative Medical Sciences Laboratory for Bone and Joint Diseases

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

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Research Summary

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 25 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 Fields

Medicine, Dentistry & Pharmacy

Related Research Fields

Biological Sciences

Keywords

Bone and joint disease
genome
Association study
Genetic disease
Intractable disease

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)