Cell Induction and Regulation

kao Noriyuki Tsumaki, M.D., Ph.D.  btn

Growth plate cartilage is where bone grows, and articular cartilage sustains smooth joint movement. We have been investigating the mechanisms controlling the proliferation and differentiation of chondrocytes. Based on the findings obtained, we are trying to regenerate cartilage and analyze locomotive diseases using a combination of cell reprogramming technologies. However, many issues remain unresolved, and there are currently no effective therapies available for cartilage diseases. In our lab, we think outside the box, discuss all options and are doing research to solve the issues related to skeletal research.

Research and Education

The research project currently underway in our lab fall into three categories:
1) We are analyzing the molecular mechanisms that control the proliferation and differentiation of chondrocytes, and thereby maintain normal cartilage tissue.
2) We are investigating skeletal dysplasias which are caused by abnormalities in growth plate cartilage using disease modeling employing iPS cells. We generate iPS cells from patients’ fibroblasts, differentiate them into chondrocytes, and then use the resulting cells to analyze the pathomechanics of the disease and search for drug candidates.
3) We are trying to regenerate injured and/or degenerated articular cartilage. We have been transplanting chondrocytes generated by the differentiation of iPS cells into the articular cartilage defects created in animal models. As another approach, we have been investigating the in vivo direct reprogramming of cells in degenerated cartilage into healthy chondrocytes.
Students are instructed by the professor and three researchers. Meetings are held regularly. Research strategies and how to give presentations are also a focus of the instruction.

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Fig. 1 Cartilage generated in mouse. Skin fibroblasts were directly reprogrammed into chondrocytes and transplanted into subcutaneous tissue. Lower panels are magnification of upper panel.

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Fig. 2 Lab members


Recent Publications

1.Yamashita, A., Morioka, M., Kishi, H., Kimura, T., Yahara, Y., Okada, M., Fujita, K., Sawai, H., Ikegawa, S., and Tsumaki, N. (2014). Statin treatment rescues FGFR3 skeletal dysplasia phenotypes. Nature 513, 507-511.
2.Okada, M., Ikegawa, S., Morioka, M., Yamashita, A., Saito, A., Sawai, H., Murotsuki, J., Ohashi, H., Okamoto, T., Nishimura, G., et al. (2014). Modeling type II  collagenopathy skeletal dysplasia by directed conversion and induced pluripotent stem cells. Hum Mol Genet. In press
3.Minegishi Y, Hosokawa K, Tsumaki N. Time-lapse observation of the dedifferentiation process in mouse chondrocytes using chondrocyte-specific reporters. Osteoarthritis Cartilage, 2013; 21: 1968-1975. (doi:10.1016/j.joca.2013.09.004)
4.Hiramatsu, K., Sasagawa, S., Outani, H., Nakagawa, K., Yoshikawa, H. and Tsumaki, N.: Generation of hyaline cartilaginous tissue from mouse adult dermal fibroblast culture by defined factors. J. Clin. Invest., 121: 640-57, 2011.
5.Tsumaki, N., Kimura, T., Matsui, Y., Nakata, K. and Ochi, T.: Separable cis-regulatory elements that contribute to tissue- and site-specific alpha 2(XI) collagen gene expression in the embryonic mouse cartilage. J. Cell Biol., 134: 1573-82, 1996

Cell Induction and Regulation

Professor Noriyuki Tsumaki
Researcher Kaori Fujita
Researcher Akihiro Yamashita
Researcher Minoru Okada
TEL +81-75-366-7045
FAX +81-75-366-7047
e-mail:ntsumaki@cira.kyoto-u.ac.jp
URL:http://www.cira.kyoto-u.ac.jp/e/research/tsumaki_summary.html