Department of Molecular Biology and Biochemistry

The extracellular matrix (ECM) plays a major role for supporting cells. ECM macromolecules are secreted
locally by the cells to wear “tailor-made” ECMs for their suitable conditions in a tissue-dependent or a timedependent manner.
The Department of Molecular Biology and Biochemistry is addressing the role of ECM during physiologicalsituations such as development and tissue repair and pathological situations. To reach this goal we alter
ECM molecules-functions in vivo using genetically altered mice. In particular we modify the molecularassembly of ECM components by deleting the core assembling molecules, introducing site-specificmutations into molecules and deleting proteolytic enzymes etc. We hope to develop our basic findings into
clinical outcomes in future.

• Role of perineuronal nets (PNN) in the control of plasticity

and pathogenesis of psychiatric disorders
PNNs are unique extracellular matrix structures that wrap around certain neurons in
the CNS during development and control plasticity in the adult CNS. They appear tocontribute to a wide range of diseases/disorders of the brain and are altered during
aging, learning and memory, and after exposure to drugs of abuse (Sorg et al., J
Neurosci 2016).
Our focus is on how the condensation of PNN is important during development and on
the protective role of PNN in neural functions that may relates to synaptic pathology.

• Role of basement membrane in tissue repair
Basement membrane (BM) have been recognized as important regulator of cell
behavior, rather than just structural features of tissue. BMs are crucial for tissue
homeostasis and are implicated in important biological processes such as
development, regeneration and repair. We are focusing on physiological tissue repair.
Understanding the molecular underpinnings of these process is expected to offer
insights into new treatment approaches for tissue repair.

• Role of basement membrane during tooth development
We have recently demonstrated the possibility of regenerating lost teeth themselves.
In a first large-animal study, bioengineered tooth germs were transplanted into thejawbone of dogs. Like a regular tooth, the growing cells formed a bioengineered
tooth that erupted through the gum, and could be orthodontically moved withbrackets. This result suggests whole-tooth regeneration using tooth germ cells
derived from a patient’s own cells may become possible. Now our focus is tounderstand the tooth development from the point of view of basement membrane.

• Therapy for bone regeneration using E. coli-BMP-2
Bone morphogenetic protein 2 (BMP-2) is one of most attractive cytokine toregenerate bone. In order to overcome the costly treatment using the currently
available cell-derived BMP-2, we are collaborating with a Japanese start-up company
to develop a low-cost Escherichia coli-based system to produce BMP-2. Recent
studies in large animals have demonstrated the safety and efficacy of thisrecombinant BMP-2 for regenerating alveolar bone. We are close to completing therequirements for the use of E. coli-BMP-2 in a clinical trial with human subjects.
Department of Molecular Biology and Biochemistry (Toshitaka Oohashi, 大橋俊孝)
Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama 700-8558, Japan
E-mail: oohashi@cc.okayama-u.ac.jp TEL: +81-86-235-7127 FAX: +81-86-222-7768

Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences