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Laboratory for Bone and Joint Diseases
Shiro IKEGAWA
Laboratory Head
Shiro IKEGAWA (M.D., Ph.D.)

Research Areas

Identifying the genetic factors for lifestyle diseases affecting bones and joints and uncovering the secret of skeletal formation
Overcoming bone and joint diseases has become a major global concern, as witnessed by the initiative of World Health Organization (WHO), The Bone and Joint Decade. In Japan alone, 10 million patients suffer from osteoarthritis (a degenerative condition of the joints of the hand, leg and back), which can cause pain and difficulty walking. Over 30% of Japanese over the age of 70 suffer from osteoarthritis and the disease progresses rapidly with age, making it a serious concern because of the rapid aging of Japanese population. Moreover, more than 1% of Japanese suffer from degenerative disc disease including lumbar disc herniation, which is the main cause of back pain and neurogenic leg pain for people in their prime working years. Unfortunately, a fundamental treatment has not been established, as there has been limited research on the causes of such bone and joint diseases, compounded with a lack of understanding of the pathological mechanisms involved.

The Laboratory for Bone and Joint Diseases uses genetic polymorphism analysis as a starting point for advancing mechanistic understanding of bone and joint diseases. During the last couple of years, we successfully identified GDF5 as a novel causative gene in osteoarthritis, and COL11A1, TBSP2 and MMP9 as novel causative genes in disc herniation. As part of international research collaboration, we have also confirmed that asporin (another gene first identified by our group) and GDF5 are ethnicity-independent risk factors contributing to the pathogenesis of osteoarthritis. Furthermore, using an integrated mouse and human genetics approach, we discovered a novel gene, SLC35D1, required for skeletogenesis. We also demonstrated that SLC35D1 is a causative gene for Schneckenbecken dysplasia in human. Apart from elucidating the mechanisms of these genes, our laboratory is currently aiming to develop new preventive strategies and groundbreaking treatment by identifying the molecular pathogenesis of the bone and joint diseases.

Research Subject

  1. Genetic analysis of skeletal dysplasias
  2. Clarification of mechanism of skeletal formation and regenerative medicine of skeletal tissues
  3. Identification of disease genes for common bone and joint diseases
  4. Regenerative medicine
  5. Order-made medicine

Related links

  1. RIKEN Center for Genomic Medicine Website_Laboratories PageNew Window

List of Selected Publications

  1. 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).
  2. Rock, MJ., Prenen, J., Funari, VA., Funari, TL., Merriman, B., Nelson, SF., Lachman, RS., Wilcox, WR., Reyno, S., Quadrelli, R., Vaglio, A., Owsianik, G., Janssens, A., Voets, T., Ikegawa, S., Nagai, T., Rimoin, DL., Nilius, B., and Cohn, DH.:
    "Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia."
    Nat Genet 40(8):999-1003, (2008).
  3. Ozaki, K., Sato, H., Inoue, K., Tsunoda, T., Sakata, Y., Mizuno, H., Lin, TH., Miyamoto, Y., Aoki, A., Onouchi, Y., Sheu, SH., Ikegawa, S., Odashiro, K., Nobuyoshi, M., Juo, SH., Hori, M., Nakamura, Y., and Tanaka, T.:
    "SNPs in BRAP associated with risk of myocardial infarction in Asian populations."
    Nat Genet 41(3):329-33, (2009).
  4. Fukada, T., Civic, N., Furuichi, T., Shimoda, S., Mishima, K., Higashiyama, H., Idaira, Y., Asada, Y., Kitamura, H., Yamasaki, S., Hojyo, S., Nakayama, M., Ohara, O., Koseki, H., Dos, Santos, HG., Bonafe, L., Ha-Vinh, R., Zankl, A., Unger, S., Kraenzlin, ME., Beckmann, JS., Saito, I., Rivolta, C., Ikegawa, S., Superti-Furga, A., and Hirano, T.:
    "The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways."
    PLoS ONE 3(11): e3642, (2008).
  5. Hirose, Y., Chiba, K., Karasugi, T., Nakajima, M., Kawaguchi, Y., Mikami, Y., Furuichi, T., Mio, F., Miyake, A., Miyamoto, T., Ozaki, K., Takahashi, A., Mizuta, H., Kubo, T., Kimura, T., Tanaka, T., Toyama, Y., and Ikegawa, S.:
    "A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation."
    Am J Hum Genet 82(5):1122-9, (2008).
  6. Song, YQ., Cheung, KM., Ho, DW., Poon, SC., Chiba, K., Kawaguchi, Y., Hirose, Y., Alini, M., Grad, S., Yee, AF., Leong, JC., Luk, KD., Yip, SP., Karppinen, J., Cheah, KS., Sham, P., Ikegawa, S., and Chan, D.:
    "Association of the asporin D14 allele with lumbar-disc degeneration in Asians."
    Am J Hum Genet 82(3):744-7, (2008).
  7. Chapman, K., Takahashi, A., Meulenbelt, I., Watson, C., Rodriguez-Lopez, J., Egli, R., Tsezou, A., Malizos, KN., Kloppenburg, M., Shi, D., Southam, L., van der Breggen, R., Donn, R., Qin, J., Doherty, M., Slagboom, PE., Wallis, G., Kamatani, N., Jiang, Q., Gonzalez, A., Loughlin, J., and Ikegawa, S.:
    "A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5' UTR of GDF5 with osteoarthritis susceptibility."
    Hum Mol Genet 17(10):1497-504, (2008).
  8. Mototani, H., Iida, A., Nakajima, M., Furuichi, T., Miyamoto, Y., Tsunoda, T., Sudo, A., Kotani, A., Uchida, A., Ozaki, K., Tanaka, Y., Nakamura, Y., Tanaka, T., Notoya, K., and Ikegawa, S.:
    "A functional SNP in EDG2 increases susceptibility to knee osteoarthritis in Japanese."
    Hum Mol Genet 17(12):1790-7, (2008).
  9. Meulenbelt I, Min JL, Bos S, Riyazi N, Houwing-Duistermaat JJ, van der Wijk HJ, Kroon HM, Nakajima M, Ikegawa S, Uitterlinden AG, van Meurs JB, van der Deure WM, Visser TJ, Seymour AB, Lakenberg N, van der Breggen R, Kremer D, van Duijn CM, Kloppenburg M, Loughlin J, Slagboom PE.
    "Identification of DIO2 as new susceptibility locus for symptomatic osteoarthritis."
    Hum Mol Genet 17(12):1867-75, 2008.
  10. Fukui, N., Miyamoto, Y., Nakajima, M., Ikeda, Y., Hikita, A., Furukawa, H., Mitomi, H., Tanaka, N., Katsuragawa, Y., Yamamoto, S., Sawabe, M., Juji, T., Mori, T., Suzuki, R., and Ikegawa, S.:
    "Zonal gene expression of chondrocytes in osteoarthritic cartilage."
    Arthritis Rheum 58(12):3843-53, (2008).
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