2009 Fiscal Year Final Research Report
Therapeutic effect of Chondroitinase ABC and Keratanase for spinal cord injury
| Project/Area Number |
20791029
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
IMAGAMA Shiro Nagoya University, 医学部附属病院, 助教 (40467288)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 脊髄損傷 / プロテオグリカン / コンドロイチン硫酸 / ケラタン硫酸 / プロテオグリカン分解酵素 / ケラタナーゼ / 運動機能回復 / 齧歯類 |
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| Research Abstract |
Failure of axonal regrowth is a major obstacle to the treatment of injuries of the adult central nervous system, and proteoglycans are strong inhibitory cues. Chondroitin sulfate chains of the proteoglycan moiety have been thought to be principal in this inhibition, as the chondroitin sulfate-degrading enzyme chondroitinase ABC promotes functional recovery after spinal cord injury. Here we show that the keratan sulfate-degrading enzyme keratanase II promoted the recovery of both motor and sensory function after spinal cord injury in rats. Consistent with this, keratanase II promoted axonal regrowth in vivo and in vitro. Unexpectedly, keratanase II and chondroitinase ABC exerted comparable effects in vivo and in vitro, but these two enzymes worked neither additively nor synergistically. Neurite outgrowth was inhibited by the keratan sulfate/chondroitin-proteoglycan aggrecan but not by an artificial proteoglycan, keratan sulfate/chondroitin-albumin, or by heat-denatured proteoglycans. Our data indicate that keratan sulfate is required for the inhibitory property of proteoglycans and is a candidate target for therapy of neuronal injuries.
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