Department of Biochemistry and Molecular Biology

Tissue Biochemistry

Understanding regulatory mechanisms for cell and tissue differentiation to study and treat diseases
  • Understanding molecular mechanisms that regulate bone and cartilage formation
  • Developing regenerative treatments for articular cartilage damage
  • Discovering drugs that cure growth cartilage abnormalities

Professor Noriyuki Tsumaki
Tissue Biochemistry,
Department of Biochemistry and Molecular Biology,
Graduate School of Medicine
The skeleton is made of cartilage, which includes articular cartilage and growth cartilage. Abnormalities in articular cartilage cause joint dyskinesia (mobility impairment), while abnormalities in growth cartilage cause skeletal growth disorders.The treatment of these cartilage diseases is difficult and has been a challenging area of research for many years. In our laboratory, we are attempting to elucidate the pathogenesis of cartilage diseases by investigating the mechanisms that control cartilage formation and differentiation using biochemistry, molecular biology, and histology techniques.We are also working on the development of new cartilage regeneration therapies and drug discovery using iPS cell technology.

We aim to understand the mechanisms of cell and tissue differentiation at the molecular level to control related pathologies and develop curative treatments


The skeleton and joints are indispensable for animals, including humans, to move their bodies. They are made from cartilage through a process called endochondral bone formation. Cartilage diseases thus impair skeletal formation and movements, but many have no curative treatments.Cartilage is tissue that consists of chondrocytes and cartilage extracellular matrix. Both are needed for cartilage to achieve its normal function. Our laboratory is investigating the mechanisms responsible for cartilage tissue formation by analyzing chondrocyte signaling and the function of matrix genes (J Cell Biol 1996; 1999; 2004; J Clin Invest 2011; Nature Commun 2016).

As one approach, we employ genetically modified mice and analyze their phenotypes using biochemistry, molecular biology and histology techniques. Based on the findings obtained through such basic science research, we are developing curative treatments for cartilage diseases.
We have also developed methods which induce iPS cells to differentiate into chondrocytes that produce cartilage extracellular matrix and ultimately grow into cartilage tissue (Nature 2014; Stem Cells Transl Med 2020).
Transplantation experiments using this iPS cell-derived cartilage are being conducted as regenerative medicine for cartilage damage. For skeletal dysplasia, we are building cartilage models based on patient-specific iPS cells and conducting drug screening (Osteoarthritis Cartilage 2018; Sci Rep 2020).

We are analyzing the biological materials not as cells but as tissues consisting of cells and extracellular matrices to try and understand at the molecular level how tissues differentiate. Crucial to our approach is the combination of genetically modified mice, cell reprogramming, gene editing and single cell RNA-sequencing. By clarifying the pathologies at the molecular level, we aim to develop curative treatments for intractable diseases.