The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury

Journal of Neuroinflammation

Kenji Kadomatsu²  Naoki Ishiguro³  Yukihiro Matsuyama¹  Ryuichi Shinjo³  Akio Muramoto³  Tomohiro Ohgomori²  Takamitsu Natori²  Shiro Imagama³  Ryoji Tauchi³ 

[1] Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan;Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan;Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan

关键词: Rat;    Keratan sulfate proteoglycan;    Chondroitin sulfate proteoglycan;    Extracellular matrix;    Spinal cord injury;    ADAMTS-4;   

Others  :  1212726
DOI  :  10.1186/1742-2094-9-53

 received in 2011-07-30, accepted in 2012-03-15,  发布年份 2012

【 摘 要 】

Background

Chondroitin sulfate proteoglycans are major inhibitory molecules for neural plasticity under both physiological and pathological conditions. The chondroitin sulfate degrading enzyme chondroitinase ABC promotes functional recovery after spinal cord injury, and restores experience-dependent plasticity, such as ocular dominance plasticity and fear erasure plasticity, in adult rodents. These data suggest that the sugar chain in a proteoglycan moiety is essential for the inhibitory activity of proteoglycans. However, the significance of the core protein has not been studied extensively. Furthermore, considering that chondroitinase ABC is derived from bacteria, a mammalian endogenous enzyme which can inactivate the proteoglycans' activity is desirable for clinical use.

Methods

The degradation activity of ADAMTS-4 was estimated for the core proteins of chondroitin sulfate proteoglycans, that is, brevican, neurocan and phosphacan. To evaluate the biological significance of ADMATS-4 activity, an in vitro neurite growth assay and an in vivo neuronal injury model, spinal cord contusion injury, were employed.

Results

ADAMTS-4 digested proteoglycans, and reversed their inhibition of neurite outgrowth. Local administration of ADAMTS-4 significantly promoted motor function recovery after spinal cord injury. Supporting these findings, the ADAMTS-4-treated spinal cord exhibited enhanced axonal regeneration/sprouting after spinal cord injury.

Conclusions

Our data suggest that the core protein in a proteoglycan moiety is also important for the inhibition of neural plasticity, and provides a potentially safer tool for the treatment of neuronal injuries.

【 授权许可】

   
2012 Tauchi et al; licensee BioMed Central Ltd.

【 图 表 】

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