Cellular Differentiation

kao Yuji Hiraki, Ph,D. Professor btn

With the advent of the aging society, movement disorder is becoming the major targets in modern health care and medicine. Our research efforts are focused on the elucidation of molecular mechanisms underlying formation and regeneration of tissues in locomotive organs such as bone, cartilage, and tendon/ligaments with the molecular approaches based on developmental biology and cell biology.

Research and Education

Tissues of mesenchymal origin contain a well-developed network of capillaries. However, cartilage is considerably resistant to vascular invasion from surrounding soft tissues and is kept avascular except at the stage of vascular invasion into cartilaginous bone molds during endochondral bone development in embryos. Tendons and ligaments are also known to be hypovascular tissues. These tissues exhibit very poor regenerative capacity after injury or under degenerative pathological conditions. This is why these tissues have been important targets in regenerative medicine. In our laboratory, we identified chondromodulin-I for the first time as a tissue-specific angiogenesis inhibitor in cartilage. Searching the chondromodulin-I related gene enabled us to identify another anti-angiogenic molecule termed Tenomodulin, which is specifically expressed in tendons and ligaments. Through molecular analyses of these physiological angiogenesis inhibitors, we are aiming at understanding what the nature of avascularity is in mesenchymal structures and how it plays a role during development and repair of musculoskeletal organs.

r-086-1

Lineage determination and differentiation of mesenchymal cells regulated by the specific transcription factors.

r-086-2

People in Hiraki Laboratory (at the front gate of Fushimi Inari Shrine)

Recent Publications

1.Takimoto A, Kawatsu M, Yoshimoto Y, Kawamoto T, Seiryu M, Takano-Yamamoto T, Hiraki Y, Shukunami C (2015) Scleraxis and Osterix antagonistically regulate tensile force-responsive remodeling of the periodontal ligament and alveolar bone. Development, 142: 787-796.

2.Miura S, Kondo J, Takimoto A, Sano-Takai H, Guo L, Shukunami C, Tanaka H, Hiraki Y (2014) The N-terminal cleavage of Chondromodulin-I in growth-plate cartilage at the hypertrophic and calcified zones during bone development. PLoS One, 9(4): e94239.

3.Sugimoto Y, Takimoto A, Akiyama H, Kist R, Scherer G, Nakamura T, Hiraki Y, Shukunami C (2013) Scx+/Sox9+ progenitors contribute to the establishment of the junction between cartilage and tendon/ligament. Development, 140: 2280-2288.

4.Takimoto A, Oro M, Hiraki Y, Shukunami C (2012) Direct conversion of tenocytes into chondrocytes by Sox9. Exp. Cell Res., 318: 1492-1507.

5.Miura S, Mitsui K, Heishi T., Shukunami C, Sekiguchi K, Kondo J, Sato Y, Hiraki Y (2010) Impairment of VEGF-A stimulated lamellipodial extensions and motility of vascular endothelial cells by Chondromodulin-I, a cartilage derived angiogenesis inhibitor. Exp. Cell Res., 316: 775-788.

Laboratory

Professor: Yuji Hiraki
Assistant Professor:Shigenori Miura
TEL: +81-75-751-4608
FAX: +81-75-751-4633
e-mail: hiraki@frontier.kyoto-u.ac.jp
URL: http://www.frontier.kyoto-u.ac.jp/te01/index-j.htm