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 - Institute for Frontier Medical Sciences
Cellular Differentiation
Field of Tissue Engineering
With the advent of the aging society, movement disorder and dementia are becoming 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.

  Yuji Hiraki, Ph.D.
Research and Education
In general, mesenchymal tissues contain a well-developed network of capillaries. However, cartilage is resistant to vascular invasion from surrounding tissues and is usually kept avascular except for the vascular invasion into cartilage during endochondral bone formation. Similarly, tendons and ligaments are known to be hypovascular. In our laboratory, we identified chondromodulin-I for the first time as a tissue-specific angiogenesis inhibitor in cartilage. Molecular cloning of the chondromodulin-I related gene enabled us to identify another tissue-specific anti-angiogenic molecule Tenomodulin, which is specifically expressed in tendons and ligaments. We think it important to understand what is the nature of hypovascularity in mesenchymal structures and how it plays a role in the body during development and regeneration of musculoskeletal organs.
Our current research efforts are focused on the following studies: 1) mechanism of replacement of cartilage by bone during endochondral bone formation; 2) identification of novel genes associated with chondrogenic differentiation by global analysis of gene expression; 3) mechanism underlying regeneration of articular cartilage; 4) molecular mechanism of tendon/ligament development; 5) action mechanisms of tissue-specific anti-angiogenic factors and their therapeutic applications for angiogenic diseases.

Cellular Differentiation
Institute for Frontier Medical Sciences
Professor Yuji Hiraki

Chisa Shukunami
TEL +81-75-751-4608
FAX +81-75-751-4633
Differentiation of mesenchymal stem cells
Fish facility for Medaka and Zebrafish.
Medaka and zebrafish are excellent model organisms for elucidating developmental processes due to the transparency of embryos. Current projects in our laboratory are to reveal role of chondromodulin-I, cartilage-derived angiogenesis inhibitor, in vascular development and molecular mechanism of cartilage development.
Laboratory members
Recent Publications
1. 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
2. Takimoto A, Nishizaki Y, Hiraki Y, Shukunami C (2009) Differential actions of VEGF-A isoforms on perichondrial angiogenesis during endochondral bone formation. Dev Biol 322: 196-211
3. Shukunami C, Takimoto A, Miura S, Nishizaki Y, Hiraki Y (2008) Chondromodulin-I and tenomodulin are differentially expressed in the avascular mesenchyme during mouse and chick development. Cell Tissue Res 332: 111-122
4. Mori H, Shukunami C, Furuyama A, Notsu H, Nishizaki Y, Hiraki Y (2007) The immobilization of bioactive FGF-2 into cubic proteinous micro-crystals (Bombyx mori cypovirus polyhedra) that are insoluble in a physiological cellular environment. J Biol Chem 282: 17289-17296
5. Shukunami C, Takimoto A, Oro M, Hiraki Y (2006) Scleraxis positively regulates the lineage-specific expression of tenomodulin, a marker of tenocytes. Dev Biol 298: 234-247