⎇ⓥ⺖㗴ฬ㧦࡟࡯ࠩ࡯ᾖ኿ߩ↢‛ቇ⊛ലᨐߩ⚦⢩ቇ⊛⸃᣿- ၭ㙃⚦⢩ߩㆮવሶ⊒⃻ࡊࡠࡈࠔࠗ࡝ࡦࠣߣࡄࠬ࠙ࠛࠗ⸃ᨆ ⎇ⓥઍ⴫⠪㧦቟ቊሶቱశ (ᣣᧄᄢቇ᧻ᚭᱤቇㇱᱤቇ⑼)⎇ⓥᓥ੐⠪㧦ᐔႦ ᶈ৻ (ᣣᧄᄢቇ᧻ᚭᱤቇㇱᱤቇ⑼)   ᄙ↰ ల⵨ (ᣣᧄᄢቇ᧻ᚭᱤቇㇱᱤቇ⑼)౒ห⎇ⓥ⠪ ᵿፉ ㅴ  (ᣣᧄᄢቇ᧻ᚭᱤቇㇱᱤቇ⑼)‫⎇ޣ‬ⓥ⋡⊛‫ޤ‬ ࡟࡯ࠩ࡯ᾖ኿ߪഃ்‫ޔ‬㔍ᴦᕈẩ≌ߦᴦ≹ലᨐ߇޽ࠆߣႎ๔ߐࠇߡએ᧪‫ޔ‬Ἳ∝‫ޔ‬−∩ߦኻߔࠆᛥ೙
૞↪߿㛽ᒻᚑߩଦㅴലᨐ߇⸽᣿ߐࠇߡ޿ࠆ‫৻ޔࠄ߇ߥߒ߆ߒޕ‬ᣇߢߪ࡟࡯ࠩ࡯≮ᴺߦᙬ⇼⊛ߥ⷗⸃߽ᄙߊ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߩലᨐࠍᔃℂ⊛ߥࡊ࡜࠮ࡏലᨐ߇ᄢ߈޿ߣߔࠆ⠨߃߿࡟࡯ࠩ࡯ᴦ≮ߪ‫⥃ޔ‬ᐥᔕ↪߇⹜ⴕ㍲⺋⊛ߦታᣉߐࠇߡലᨐߩ޽ߞߚ੐⽎ߛߌ߇⹶ᒛߐࠇߡ޿ࠆߣ޿߁ᗧ⷗߽޽ࠆ‫ޔߚ߹ޕ‬↢‛ቇ⊛ലᨐߪනߥࠆ᷷ᐲ਄᣹ലᨐߦࠃࠆ߽ߩߢ޽ࠈ߁ߣߔࠆ⼏⺰߿࡟࡯ࠩ࡯ᾖ኿ߩ೽૞↪ߦߟ޿ߡචಽᬌ⸛ߐࠇߡ޿ߥ޿ߣ޿߁ᜰ៰߽ߐࠇߡ޿ࠆ‫࡯ࠩ࡯࡟ޔߚ߹ޕ‬ᵄ㐳ߩ㆑޿ߦࠃࠆ↢‛ቇ⊛ലᨐߦߟ޿ߡ߽ਇ᣿ߥὐ߇ᄙ޿‫ߥ߁ࠃߩߎޕ‬⢛᥊߆ࠄ࡟࡯ࠩ࡯ᾖ኿ߩ↢‛ቇ⊛ലᨐߩ૞↪ᯏᐨߩ⸃᣿
ߪᧂߛਇචಽߢ޽ࠅ‫ޔ‬Ⓧᭂ⊛ߥ⥃ᐥᔕ↪߇ᦼᓙߐࠇߡ޿ࠆߥ߆ߢ‫࡯ࠩ࡯࡟ޔ‬ක≮ࠍߐࠄߦផㅴ‫⊒ޔ‬ዷߐߖࠆߚ߼ߦߪ‫↪᦭ޔ‬ᕈߩ㜞޿࡟࡯ࠩ࡯ᾖ኿ߩᯏ⒳‫ޔ‬ᾖ኿ᴺࠍ㐿⊒ߔࠆߣߣ߽ߦ‫‛↢ޔ‬ቇ⊛ലᨐࠍታ⸽⑼ቇ⊛ߦ⸃᣿ߒߡ޿ߊᔅⷐ߇޽ࠆߣᕁࠊࠇࠆ‫ޕ‬ ᧄ⎇ⓥߢߪ‫ޔ‬ᱤ⡺✢⛽⧘⚦⢩‫ޔ‬㑐▵࡝ࡘ࠙ࡑ࠴ߩ⤒Ṗ⤑⚦⢩‫ޔ‬㛽⧘⚦⢩ߩ⚦⢩ၭ㙃♽ࠍ↪޿ߡ࡟࡯ࠩ࡯ᾖ኿ߦࠃࠆㆮવሶ⊒⃻ᄌൻࠍࡊࡠࡈࠔࠗ࡝ࡦࠣߒ‫‛↢ޔ‬ቇ⊛ലᨐߩᯏᐨ⸃᣿ࠍ⹜ߺߚ‫ޕ‬‫⎇ޣ‬ⓥ᭎ⷐ‫ޤ‬ ᚑੱߩ㧤㧜㧑એ਄߇⟕ᖚߔࠆᱤ๟∛ߪᱤߩ༚ᄬේ࿃ߣߥࠆ‫ޕ‬㜞㦂⠪ߦ߅ߌࠆᱤ༚ᄬߩᦨᄢේ࿃ߪ
ᱤ๟∛ߢ޽ࠅ‫ޔ‬ട㦂ߦࠃࠅᱤ๟∛ߩ∛ᘒ߇ㅴዷߔࠆߣାߓࠄࠇߡ޿ࠆ‫ޔߒ߆ߒޕ‬㜞㦂⠪ߩᱤ๟∛ߪ⠧ൻߣ޿߁࿃ሶߛߌ߇ᒁ߈㊄ߣߥߞߡ⊒∝ߪߒߥ޿ߣ⠨߃ࠄࠇߡ޿ࠆ‫ޕ‬㜞㦂⠪ߩᱤ๟∛ߣ޿߃ߤ߽
ᱤ⡺Ἳ࡮ᱤ๟Ἳߩ⊒∝ߦߪ⚦⩶ᗵᨴ߇㊀ⷐߥේ࿃ߢ޽ࠆߎߣߪ㑆㆑޿ߥ޿‫ޕ‬ ࠗࡦ࠲࡯ࡠࠗࠠࡦ-1E (interleukin-1Eҏ1L-1E)ߪ‫ޔ‬ㆮવሶߩォ౮‫ޔ‬⠡⸶ᓟߪ೨㚟૕ߣߒߡ↢วᚑߐࠇ‫ޔ‬ᄌ឵㉂⚛(1L-1Econverting enzyme; ICE)ߦࠃߞߡᵴᕈဳߦߥࠆ‫ޕ‬1L-1EߪἻ∝ᕈࠨࠗ࠻ࠞࠗࡦߣߒߡ
Ἳ∝ߩㅴዷߦ㑐ਈߔࠆߣߣ߽ߦ‫ޔ‬⎕㛽⚦⢩ߩಽൻ‫ޔ‬ᵴᕈൻ࿃ሶߣߒߡ௛߈‫߽ߡߒߣ⾰‛∩⊒ޔ‬⍮ࠄࠇߡ޿ࠆ‫ ࡦࠫࡦ࡜ࠣ࠲ࠬࡠࡊޕ‬E2 (prostaglandin E2; PGE2)ߪ‫ ࠯࡯ࡄ࡝ࡎࠬࡎޔ‬A2 ߦࠃߞߡ⚦⢩⤑ߩ࡝ࡦ⢽⾰߆ࠄㆆ㔌ߐࠇࠆࠕ࡜ࠠ࠼ࡦ㉄ࠍၮ⾰ߦᓞㅦ㉂⚛ࠪࠢࡠࠝࠠࠪࠥ࠽࡯࠯ߦࠃߞߡࡊࡠࠬ࠲
ࠣ࡜ࡦࠫࡦ G2/H2 ߇วᚑߐࠇ‫ ߢ޿ߟޔ‬PGE2 วᚑ㉂⚛ߦࠃߞߡวᚑߐࠇࠆ‫ޕ‬PGE2 ⴊ▤ㅘㆊᕈଦㅴ࿃
ሶߣߒߡἻ∝ߩㅴዷߦ㑐ਈߔࠆߣߣ߽ߦ‫ޔ‬⎕㛽⚦⢩ߩಽൻ‫ޔ‬ᵴᕈൻ࿃ሶߣߒߡ௛߈‫ߩ∩⊒ޔ‬ଦㅴ‛⾰ߣߒ߽⍮ࠄࠇߡ޿ࠆ‫ޕ‬ ߘߎߢ‫⩶⚦ޔ‬ᗵᨴߦኻߔࠆ㒐ᓮ⚵❱ߣߒߡߩⷰὐ߆ࠄᱤ๟∛ේ⚦⩶ౝᲥ⚛(LPS)ߢੱᱤ⡺✢⛽⧘⚦⢩ࠍೝỗߔࠆၭ㙃⚦⢩♽ߢ PGE2‫ޔ‬IL-1EߩἻ∝ࡔ࠺ࠖࠛ࡯࠲࡯↥↢߇⺃ዉߐࠇࠆታ㛎ࡕ࠺࡞♽ࠍ⸳ቯߒߚ‫ߩߎޕ‬ၭ㙃ታ㛎♽ࠍᔕ↪ߒߡ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߩᓇ㗀ࠍ⺞ߴߚ‫⚿ߩߘޕ‬ᨐ‫ޔ‬LPS ೝỗߢჇᄢߒߚ PGE2‫ޔ‬IL-1E↥↢㊂ߪ޿ߕࠇ߽࡟࡯ࠩ࡯ᾖ኿ߦࠃߞߡᷫዋߒߡ޿ߚ‫ߩߎޕ‬ലᨐߪᾖ኿㊂ߦଐሽߒߡ߅ࠅ‫↢↥ޔ‬ᛥ೙ߪ COX2 ߣ IL-1Eߩㆮવሶ⊒⃻ߩᛥ೙ߦࠃࠅ⿠ߎߞߡ޿ࠆߎߣ߇᣿ࠄ߆ߣߥߞ

ߚ‫ޔߚ߹ޕ‬㑐▵࡝ࡘ࠙ࡑ࠴ߩ⤒Ṗ⤑⚦⢩ࠍ IL-1Eߢೝỗߒߚࡕ࠺࡞ታ㛎♽߳ߩ࡟࡯ࠩ࡯ᾖ኿ߪ‫ࠠޔ‬ࡕࠞࠗࡦ⟲ߩㆮવሶ⊒⃻࡟ࡌ࡞ࠍᛥ೙ߔࠆߎߣࠍ᣿ࠄ߆ߦߒߚ‫ޕ‬ ࡟࡯ࠩ࡯ᾖ኿ߦࠃࠆ㛽᛬߿㛽ᰳ៊ㇱߩ㛽ᒻᚑଦㅴ૞↪߇ႎ๔ߐࠇߡ޿ࠆ߇‫ߩߘޔ‬૞↪ᯏᐨߪ⸃᣿
ߐࠇߡ޿ߥ޿‫ޕ‬ᚒ‫ޔߪޘ‬㛽⧘⚦⢩߳ߩ࡟࡯ࠩ࡯ᾖ኿ߦࠃࠅ㛽⚿▵ᢙ‫✚ޔ‬㕙Ⓧ߇Ⴧᄢߒ‫ޔ‬ၭ㙃ᣧᦼߩ࡟࡯ࠩ࡯ᾖ኿߇ࠃࠅᒝ޿㛽ᒻᚑଦㅴലᨐࠍߔࠆߎߣ߆ࠄ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߪᧂಽൻ㑆⪲♽⚦⢩ߩჇᱺߣ㛽⧘⚦⢩߳ߩಽൻࠍଦㅴߔࠆߎߣߦࠃࠅᒁ߈⿠ߎߐࠇߡ޿ࠆߎߣࠍ⷗಴ߒߡ޿ࠆ߇‫ߩ࡯ࠩ࡯࡟ޔ‬↢‛ቇ⊛ലᨐߦ㑐ਈߔࠆࡔࠞ࠾࠭ࡓߪ߽ߞߣᄙ᭽ߢ਌ߟⶄ㔀ߢ޽ࠅ‫ᧂޔ‬⍮ߩ↢๮⃻⽎߇㑐ࠊߞߡ޿ࠆ‫࡯ࠩ࡯࡟ޔߢߎߘޕ‬ᾖ኿ߒߚ⚦⢩߆ࠄ mRNA ࠍಽ㔌ߒߡ cDNA ㆮવሶࡃࡦࠢࠍ૞ᚑߒ‫ޔ‬㕖࡟࡯ࠩ࡯ᾖ኿⚦⢩߆ࠄ࿁෼ߒߚ mRNA ࠍ↪޿ߡห৻ㆮવሶࠍᏅߒᒁߊᏅಽൻㆮવሶࠢࡠ࡯࠾ࡦࠣࠍⴕ
޿‫ޔ‬Ꮕಽൻㆮવሶ࡜ࠗࡉ࡜࡝࡯ߩฦㆮવሶࠢࡠ࡯ࡦߩႮၮ㈩೉ࠍ⸃⺒ߒߡࠥࡁࡓ࠺࡯࠲ࡌ࡯ࠬߩㆮ
વሶ㈩೉ߣࡎࡕࡠࠫ࡯ᬌ⚝ߔࠆߎߣߦࠃߞߡᒰ⹥ㆮવሶࠍหቯߒߚ‫ޕ‬ MCM (minichromosome maintenance) ㆮવሶࡈࠔࡒ࡝࡯ߪ⚦⢩ߩ⚦⢩ಽⵚᤨߦ⚦⢩๟ᦼ S ᦼߢ
DNA ⶄ⵾߇⿠ߎࠆߎߣࠍ଻⸽ߔࠆ࡜ࠗ࠮ࡦࠬ࿃ሶߢ⌀ᩭ⚦⢩ߩ DNA ⶄ⵾ߦᔅ㗇ߢ޽ࠆߎߣ߇᣿
ࠄ߆ߦߥߞߡ޿ࠆ‫ ޕ‬Northern blot ಽᨆࠍⴕߞߚߣߎࠈ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ᓟ࡟࡯ࠩ࡯㕖ᾖ኿⚦⢩ߦᲧセߒߡ MCM mRNA ࡟ࡌ࡞ߩჇട߇⹺߼ࠄࠇ‫ޔ‬DNA วᚑ⢻ࠍ᡼኿ᕈ࠴ࡒࠫࡦขࠅㄟߺ㊂ߦࠃࠅᬌ⸛ߒߚ⚿ᨐ‫࡯ࠩ࡯࡟ޔ‬㕖ᾖ኿⟲ߦᲧセߒߡჇട߇⹺߼ࠄࠇߚ‫࡯ࠩ࡯࡟ࠄ߆ߣߎߩߎޕ‬ᾖ኿ߩ⚦⢩Ⴧᱺଦㅴ૞↪ߪ MCM ㆮવሶ⊒⃻੺ߒߡ DNA ⶄ⵾ࠍㅴⴕߐߖࠆߎߣ߇㑐ਈߔࠆߎߣ߇␜ໂߐࠇߚ‫ޕ‬߹ߚ‫ޔ‬㛽⧘⚦⢩ߩ㛽ᒻᚑ૞↪ߦ㑐ㅪߔࠆㆮવሶߣߒߡ Annexin III ߣ MIF(macrophage migration
inhibitory factor)ㆮવሶࠍหቯߒ‫ޔ‬RT-PCR ᴺߦࠃߞߡ⏕⹺ߒߡߒߚ‫ޕ‬Annexin III ߪ‫⚦ޔ‬⢩ࠞ࡞ࠪ࠙ࡓߩ⺞▵ߦ㑐ਈߔࠆߣ޿ࠊࠇߡ߅ࠅ‫ޔ‬MIF ߪ‫ᦨޔ‬ㄭ‫ޔ‬㛽⧘⚦⢩ߦ߽↥↢ߐࠇߡ߅ࠅ‫ޔ‬㛽⧘⚦⢩ߩჇᱺ߿㛽ᡷㅧࠍ⺞▵ߔࠆᯏ⢻ࠍ߽ߟߎߣ߇␜ໂߐࠇߡ޿ࠆ‫ޕ‬ ࠥࡁࡓ࠺࡯࠲ࡌ࡯ࠬࠍᔕ↪ߒߡ‫ޔ‬⍴ᤨ㑆ߦㆮવሶ⊒⃻ᐲࠍ⸃ᨆߢ߈ࠆ DNA ࡑࠗࠢࡠࠕ࡟ࠗᴺߩ
㐿⊒߇ㅴࠎߢ޿ࠆ‫ ⚂ޕ‬3900 ㆮવሶߩ cDNA ࡑࠗࠢࡠࠕ࡟ࠗࠍᔕ↪ߒߡ㛽⧘⚦⢩ MC3T3-E1 ߦૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ࠍⴕ޿‫ޔ‬ㆮવሶ⊒⃻߇ᄌേߔࠆㆮવሶࠍࡕ࠾࠲࡝ࡦࠣߒߚ‫⚿ߩߘޕ‬ᨐ‫ޔ‬osteoglycin
mRNA ࡟ࡌ࡞߇ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߦࠃߞߡჇᄢߔࠆߎߣ߇⷗಴ߒ‫ޔ‬Real time PCR ᴺߦࠃߞߡ⏕⹺ߒߚ‫ޕ‬Osteogl㨥cin ߪ‫ޔ‬㛽⺃ዉ࿃ሶߣߒߡ♖⵾ߐࠇߚᮡຠߩ᭴ᚑᚑಽߢߣߒߡ⷗಴ߐࠇߚࡊࡠ࠹
ࠝࠣ࡝ࠞࡦߢ㛽ᒻᚑ࿃ሶߩ଻ᜬ‫ޔ‬ᯏ⢻⊒⃻ߦ㑐ਈߔࠆߎߣ߇ႎ๔ߐࠇߡ޿ࠆߎߣ߆ࠄ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߦࠃࠆ㛽⧘⚦⢩ߩ osteoglysin ↥↢ଦㅴߪ㛽ᒻᚑ⢻ߩଦㅴߦ㑐ਈߒߡ޿ࠆߣ⠨߃ࠄࠇࠆ‫ޕ‬ ࠝ࡝ࠧ࠿ࠢ࡟ࠝ࠴࠼ࠍࠟ࡜ࠬၮ᧼ߦ⋥ធวᚑߒ‫ޔ‬RNA ࠨࡦࡊ࡞ࠍૐಽሶൻߒߡࡂࠗࡉ࡝࠳ࠗ࠭
ߐߖࠆߎߣߢା㗬ᐲࠍ㜞߼ߚ Gene Chip ߇㐿⊒ߐࠇߡ޿ࠆ‫ޕ‬Gene Chip ߢ⸃ᨆߐࠇߚ⤘ᄢߥ࠻࡜ࡦ
ࠬࠢ࡝ࡊ࠻࡯ࡓ࠺࡯࠲ߪ⎇ⓥ⋡⊛ߩᣂⷙ㑐ㅪㆮવሶߩ⊒⷗ߦᄢ߈ߥࠗࡦࡄࠢ࠻ࠍਈ߃ߡ޿ࠆ‫ᦨޕ‬ㄭ‫ޔ‬⸃ᨆ࠺࡯࠲ࠍ⤘ᄢߥㆮવሶ㑆‫⾰ࠢࡄࡦ࠲ޔ‬㑆ߩ⋧੕㑐ଥ‫ޔ‬㜞ᰴ↢‛ቇ⊛ࡊࡠ࠮ࠬ㑐ଥߩ⤘ᄢߥ࠺࡯࠲ࡌ࡯ࠬߣ✂⟜⊛ߦᾖวߐߖࠆ Ingenuity Pathway Analysis ࠪࠬ࠹ࡓ߇㐿⊒ߐࠇߡ޿ࠆ‫ޔ‬Gene Chipࠍ↪޿ߡ‫࠻ࡅޔ‬㛽⧘⚦⢩߳ߩૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߦࠃߞߡ⊒⃻߇ᄌൻߔࠆㆮવሶߩ࠻࡜ࡦࠬࠢ࡝ࡊ
࠻࡯ࡓ⸃ᨆࠍ⹜ߺߚ‫⸃࡯ࠫࡠ࠻ࡦࠝޕ‬ᨆߒߚ⚿ᨐ‫⚦ޔ‬⢩ಽⵚ‫࡞࠽ࠣࠪޔ‬વ㆐㑐ㅪㆮવሶ‫ޔ‬ᚑ㐳࿃ሶ‫ޔ‬ᚑ㐳࿃ሶฃኈ૕‫࡞ࡀࡖ࠴ࡦࠝࠗޔ‬㑐ㅪ࿃ሶ‫ޔ‬Ca ⺞▵࿃ሶߥߤᄙᢙߩㆮવሶߩ⊒⃻߇࡟࡯ࠩ࡯ᾖ኿
ߦࠃߞߡᄌേߒߡ޿ࠆߎߣࠍ⷗಴ߒߚ‫ޔߦࠄߐޕ‬Ingenuity Pathway Analysis ࠪࠬ࠹ࡓߦ⸃ᨆ࠺࡯࠲
ࡌ࡯ࠬߦ࠺࡯࠲ࡑࠗ࠾ࡦࠣߒߚ⸃ᨆ⚿ᨐࠍㅍࠅ‫ޔ‬ᬌ⚝ߒ‫ޔ‬Wint/E-catenin ࠪࠣ࠽࡞♽‫ޔ‬PI3 kinase/JAKTࠪࠣ࠽࡞♽ߩ㑐ਈ߇␜ໂߐࠇߡ޿ࠆ‫ޕ‬䇼䉁䈫䉄䇽㩷 ၭ㙃⚦⢩♽ࠍᔕ↪ߒߡ࡟࡯ࠩ࡯ᾖ኿ߩ↢‛ቇ⊛ലᨐ߇⸽᣿ߐࠇ‫ߩߘޔ‬ᯏᐨߣߒߡ࡟࡯ࠩ࡯ᾖ኿ߪ
⒳‫ߩޘ‬ㆮવሶ⊒⃻ࠍᄌേߔࠆߎߣ߇᣿ࠄ߆ߣߥߞߚ‫ࡓࡁࠥޔߦࠄߐޕ‬/࠻࡜ࡦࠬࠢ࡝ࡊ࠻࡯ࡓ ࠺࡯࠲ࡌ࡯ࠬࠍᔕ↪ߒߚᏅಽൻㆮવሶࠢࡠ࡯࠾ࡦࠣ߿ cDNA ࡑࠗࠢࡠࠕ࡟ࠗ‫ޔ‬Affymetrix Gene Chip ࠍᔕ↪ߒߡ࡟࡯ࠩ࡯ᾖ኿ߦࠃࠆ⊒⃻ଦㅴߔࠆㆮવሶߩត⚝ߦ߽ᚑഞߒߚ‫޽ߪߢߣߎࠆߡࠇࠊ޿ߊ⦟ޕ‬ࠆ߇‫ޔ‬mRNA ࡟ࡌ࡞ߪᔅߕߒ߽࠲ࡦࡄࠢ⾰࡟ࡌ࡞ߣߪ৻⥌ߒߥ޿‫ޕ‬ㆮવሶ⊒⃻ࠍࡕ࠾࠲࡯ߔࠆ‫ߎޔ‬ࠇࠄߩ⎇ⓥᚑᨐߦࠃߞߡ࡟࡯ࠩ࡯ᾖ኿ߩ↢‛ቇ⊛ലᨐߩో⽩߇᣿ࠄ߆ߦߥߞߚࠊߌߢߪߥ޿‫ޕ‬ᖱႎવ㆐♽ߩ᭴ᚑಽሶߩߥ߆ߦߪ‫ޔ‬ᔅߕߒ߽࡟࡯ࠩ࡯ᾖ኿ߩೝỗߦࠃߞߡㆮવሶߩォ౮ࠍㅢߓߡ࠲ࡦࡄ
ࠢ⾰ࠍ⊒⃻ߐߖࠆᔅⷐߪߥߊ‫ߦߢߔߪߡߒߣ⾰ࠢࡄࡦ࠲߫߃଀ޔ‬ሽ࿷ߒߡ޿ࠆ߇ਇᵴᕈ⁁ᘒߢ޽ࠅ‫ޔ‬࡝ࡦ㉄ൻߐࠇߡᆎ߼ߡ૞↪ࠍ⊒ើߔࠆ߽ߩ߇޽ࠆ‫ߪ޿ࠆ޽ޕ‬ඨᷫᦼߩ㐳޿࠲ࡦࡄࠢ⾰ߢߪ㜞޿ㆮવሶ⊒⃻࡟ࡌ࡞ࠍᔅⷐߣߒߥ޿‫⸃ࡓ࡯࠻ࡊ࡝ࠢࠬࡦ࡜࠻ߡߞ߇ߚߒޕ‬ᨆߦࠃߞߡోߡߩ↢๮⃻⽎߇᣿ࠄ߆ߦߥࠆࠊߌߢߪߥ޿‫ޕ‬ੑᰴర㔚᳇ᵒേࠥ࡞ࠍࠗࡔ࡯ࠫࠕ࠽࡜ࠗࠩ࡯ߢಽᨆߒߡᮡ⊛࠲ࡦࡄࠢ⾰ࠬࡐ࠶࠻ࠍಾࠅ಴ߒߡ‫ޔ‬in gel digestion‫࠼࠴ࡊࡍޔ‬ᢿߩ♖⵾ࠍ⥄േ⊛ߦⴕ߁ࡠࡏ࠶࠻ߣ㘧ⴕᤨ㑆ဳ

⾰㊂ಽᨆᯏེࠪࠬ࠹ࡓࠍ↪޿ߡࠥࡁࡓ࠺࡯࠲ࡌ࡯ࠬ⸃ᨆ࠷࡯࡞ MASCOT ࠨ࡯࠴ࠍᔕ↪ߒߡ࡟࡯ࠩ
࡯ᾖ኿ߦࠃߞߡჇᷫߔࠆ࠲ࡦࡄࠢ⾰‫㉄ࡦ࡝ޔ‬ൻ࠲ࡦࡄࠢ⾰ߩ✂⟜⊛⸃ᨆࠍⴕߞߡ޿ࠆ‫࡯ࠩ࡯࡟ޕ‬ᾖ኿ߦࠃࠆ↢‛ቇ⊛ലᨐߩ⸃᣿ߦࡊࡠ࠹ࠝࡒࠢࠬ⎇ⓥࠍᔕ↪ߒߡ޿ࠆ‫ޕ‬ㄭ޿‫ޔ‬዁᧪‫ޔ‬㧔ࠥࡁࡓ㧕 ࠻࡜ࡦࠬࠢ࡝ࡊ࠻࡯ࡓ  ࡊࡠ࠹ࠝ࡯ࡓ ࠺࡯࠲ࡌ࡯ࠬᖱႎࠍ㚟૶ߒߚࡃࠗࠝࠗࡦࡈࠜ࡯ࡑ࠹ࠖࠢࠬ
⎇ⓥߦࠃߞߡ࡟࡯ࠩ࡯ᾖ኿ߦࠃࠆ↢‛ቇ⊛૞↪ߩో⽩߇᣿ࠄ߆ߦߥࠅ‫ࠅࠃޔ‬ലᨐ⊛ߥ࡟࡯ࠩ࡯ක≮ߩផㅴ߇ᦼᓙߢ߈ࠃ߁‫੹ޕ‬ᓟ‫ࠆߥ⇣ޔ‬ᵄ㐳ߩ⥄↱㔚ሶ࡟࡯ࠩ࡯ᾖ኿ߦࠃࠆ↢‛ቇ⊛ലᨐߩ㆑޿ߦߟ
޿ߡ࠻࡜ࡦࠬࠢ࡝ࡊ࠻࡯ࡓ-ࡊࡠ࠹ࠝ࡯ࡓ⸃ᨆ߆ࠄᓧࠄࠇࠆ࠺࡯࠲ߦࠃߞߡᖱႎવ㆐♽—ㆮવሶ⊒⃻ࠍࠦࠕ࡯ߦߒߚᦝߥࠆ⸃᣿߇ᔅⷐߢ޽ࠆ‫ޕ‬䇼⎇ⓥᬺ❣╬䇽
⊒⴫⺰ᢥ
䊶㩷⊒
A.ේ⪺
(1) M. Kawahara, S .Hamajima., M . Ohta, H. Sasahara, Y. and Abiko (2004) Effect of low-level laser
irradiation on macrophage inhibitory factor gene expression in osteoblasts, J. Jap. Soc. Oral Implantol.,
17, 3-12.
(2) S .Hamajima., K. Hiratsuka, M. Kiyama-Kishikawa, T. Tagawa, M. Kawahara, M. Ohta, H. Sasahara andAbiko Y: (2003) Effect of low-level laser irradiation on osteoglycin gene expression in osteoblasts.
Lasers Med. Sci.. 18,78-82;(3) ᄙ↰ల⵨‫ޔ‬ዊୖ⋥⟤‫ޔ‬ᚭㆻ⌀Ꮧሶ‫ޔ‬㈬Ꮞ⵨ਯ‫ޔ‬ౝ↰⾆ਯ‫ޔ‬ᢪ⮮ቁⷫ‫╣ޔ‬ේᑝ㊀‫ޔ‬ฬୖ⧷᣿‫ޔ‬቟ቊሶቱశ (2003) ၭ㙃ࡅ࠻㗶㑐▵Ṗ⤑⚦⢩ߦૐ಴ജ࡟࡯ࠩ࡯ᾖ኿߇෸߷ߔᓇ㗀ߦߟ޿ߡ‫ޔ‬ᣣᧄ㗶㑐▵ቇળ㔀⹹ 15, 49-54,.
(4) ᄙ↰ల⵨‫ޔ‬ዊୖ⋥⟤‫ޔ‬ᚭㆻ⌀Ꮧሶ‫ޔ‬㈬Ꮞ⵨ਯ‫ޔ‬ౝ↰⾆ਯ‫ޔ‬ᢪ⮮ቁⷫ‫╣ޔ‬ේᑝ㊀‫ޔ‬ฬୖ⧷᣿‫ޔ‬቟ቊሶቱశ‫᧻ޔ‬੗ᄢ (2003) ၭ㙃㗶㑐▵Ṗ⤑⚦⢩ߦㄭ⿒ᄖᾖ኿߇෸߷ߔᓇ㗀ߦߟ޿ߡ‫ޔ‬ᣣᧄ࡟࡯ࠩ
࡯ᱤቇળ㔀⹹‫ޔ‬14,18-24.
(5) M. Yamamoto, M. Kawahara, and Y. Abiko (2002) Enhanced gene expression by low-level laser
irradiation in osteoblast, -Identification of annexin III gene by subtractive gene cloning-, J. Jap. Soc. Oral
Implantol., 15, 323-329.
(6) ቟ቊሶቱశ㧦Ꮕಽൻㆮવሶࠢࡠ࡯࠾ࡦࠣߦࠃࠆ㛽⧘⚦⢩߳ߩૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߩ↢‛ቇ⊛ലᨐߩᯏᐨ⸃᣿‫ޔ‬ᣣᧄ࡟࡯ࠩ࡯ᱤቇળ⹹‫ޔ‬13:79-88, 2002.
(7) M. Yamamoto M, Tamura, . K. Hiratsuka, Y. and Abiko (2002) Stimulation of MCM3 gene expression in
osteoblast by low level laser irradiation. Lasers Med. Sci., 16, 213-217.
(8) K. Nomura, M. Yamaguchi, and Y. Abiko (2001) Inhibition of interleukin 1E production expression in
gingival fibroblasts by low-energy laser irradiation. Lasers Med. Sci., 16, 218-223.
(9) Y. Sakurai, M. Yamaguchi, and Y. Abiko (2000) Inhibitory effect of low-level laser irradiation on
LPS-stimulated prostaglandin E2 production and cyclooxygenase-2 in human gingival fibroblasts. Eur.
J .Oral Sci., 108:29-34, 2000.
B ⪺ᦠ(1) M. Ohta, N. Ogura, M. Tobe, H. Sakamaki, K. Ide, H. Sasahara, and Y. Abiko (2003) Effect of polarized
light near-infrared irradiation on chemokines production in synovial cells from human
temporomandibular joint, pp409-412,. in Laser in Dentistry, Revolution of Dental Treatment in the newmillennium; Excerpta Medica, International Congress Series 1248, Editors; Ishikawa, I, Frame JW, Aoki
A, ELSRVIER.
(2) Y. Abiko, K. Hiratsuka, S. Hamajima, M. Ohta, Ide K, and. H. Sasahara (2003): Genome science-based
gene expression monitoring in osteoblasts altered by low-level laser irradiation, pp433-436., in Laser in
Dentistry, Revolution of Dental Treatment in the new millennium; Excerpta Medica, International
Congress Series 1248, Editors; Ishikawa, I, Frame JW, Aoki A, ELSRVIER.

C. ✚⺑⺰ᢥ(1) ቟ቊሶቱశ (2000) ᱤ⑼ᴦ≮ߩ⃻႐ߦ߅ߌࠆ࡟࡯ࠩ࡯ߩᔕ↪‫ޔ‬ૐ಴ജߦࠃࠆ↢‛ቇ⊛ലᨐߩࡔࠞ
࠾࠭ࡓ‫ޔ‬శࠕ࡜ࠗࠕࡦࠬ 12㧦47г51.
(2) ቟ቊሶቱశ (2003) ↢ᵴ⠌ᘠ∛ߣߒߡߩᱤ๟∛ኻ╷‫ޔ‬Ἳ∝ߩᛥ೙‫ޔ‬Quintessence, 22: 932-936.
(3) ቟ቊሶቱశ(2005):࡟࡯ࠩ࡯ᾖ኿ߩ↢‛ቇ⊛ലᨐߩ⸃᣿ߣᯏ⢻ࠥࡁࡓ⑼ቇ‫ޔ‬ᣣᧄ࡟࡯ࠩ࡯කቇળ
⹹, 25:313-322.
(4) ቟ቊሶቱశ (2005) ၭ㙃⚦⢩䊧䊔䊦䈎䉌䉂䈢ૐ಴ജ䊧䊷䉱䊷ᾖ኿䈱−∩ᛥ೙ലᨐ䇮䊕䉟䊮䉪䊥䊆䉾䉪䇮
2:230-236.
࡮ቇળ⊒⴫(1) Y. Abiko, I. Ishikawa I: (2000) Lasers in Dentistry (Symposium), 22ndAsia-Pasific Dental Congress,
Tokyo.
(2) Y. Abiko (2000) Genome Science and Its Use in Dental Science, General Meeting for Korean Division ofInternational Association for Dental Research (Special lecture),. Seoul, Korea..
(3) ቟ቊሶቱశ (2001) Ꮕಽൻㆮવሶࠢࡠ࡯࠾ࡦࠣࠍᔕ↪ߒߚૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߩ↢‛ቇ⊛ലᨐߩᯏᐨ⸃᣿, ᣣᧄ࡟࡯ࠩ࡯ᱤቇળ✚ળ 㧔⑔ፉ⋵㇭ጊᏒ㧕(4) Y. Abiko (2002) Study on the mechanism of biostimulatory effect by low level laser irradiation,
Symposium for laser and oral mucosal diseases (Special lecture), Taipei, Taiwan.
(5) ቟ቊሶቱశ‫ޔ‬ᄙ↰ల⵨, ╣ේᐢ㊀ (2002) ࠥࡁࡓ⑼ቇࠍၮ⋚ߣߒߚ㛽⧘⚦⢩ߩૐ಴ജ࡟࡯ࠩ࡯ᾖ
኿ߦࠃࠆㆮવሶ⊒⃻ᄌൻߩᬌ⚝, ᣣᧄ࡟࡯ࠩ࡯ᱤቇળ✚ળ (᧲੩)(6) M. Ohta, K. Ide, N. Ogura, M. Tobe, H. Sakamaki, H. Sasahara, and Y. Abiko (2003) Effect of
Low-Level Laser Irradiation on IL-8 Production in Synovial Cells from Human Temporomandibular Joint,
8th International. Congress for Lasers in Dentistry, Yokohama..
(7) Y. Abiko, K. Hiratsuka, S. Hamajima, M. Ohta, K. Ide, and H. Sasahara (2002) Genome science-based
gene expression monitoring in osteoblasts altered by low-level laser irradiation, 8th International.
Congress for Lasers in Dentistry, Yokohama..
(8) ᄙ↰ల⵨‫ޔ‬ዊୖ⋥⟤‫ޔ‬ᚭㆻ⌀Ꮧሶ‫ޔ‬㈬Ꮞ⵨ਯ‫ޔ‬ౝ↰⾆ਯ‫ޔ‬ᢪ⮮ቁⷫ‫╣ޔ‬ේᑝ㊀ฬୖ⧷᣿‫ޔ‬቟ቊሶቱశ (2002) ၭ㙃ࡅ࠻㗶㑐▵Ṗ⤑⚦⢩ߦૐ಴ജ࡟࡯ࠩ࡯ᾖ኿߇෸߷ߔᓇ㗀ߦߟ޿ߡ‫ޔ‬ᣣᧄ㗶㑐▵ቇળ✚ળ (᧲੩)(9) ቟ቊሶቱశ (2002) ̍ஜᐽኼ๮̍ࠍᑧ߫ߔᱤ๟∛ක≮㧧↢ᵴ⠌ᘠ∛ߣߒߡߩᱤ๟∛ኻ╷‫ޔ‬Ἳ∝ߩᛥ೙, ᣣᧄቇⴚળ⼏㦏ⲁᱤ๟∛⎇ⓥㅪ⛊ળࠪࡦࡐࠫ࠙ࡓ (᧲੩)(10) ᵿፉㅴ, ᄙ↰ల⵨, ╣ේᐢ㊀, ቟ቊሶቱశ (2003) ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߩ㛽⧘⚦⢩ߦ߅ߌࠆࠝ
ࠬ࠹ࠝࠣ࡝ࠪࡦㆮવሶ⊒⃻ߦਈ߃ࠆᓇ㗀, ᣣᧄ࡟࡯ࠩ࡯ᱤቇળ✚ળ (ችၔ⋵઄บᏒ)(11) ᵿፉㅴ, ᄙ↰ల⵨, ╣ේᐢ㊀, ቟ቊሶቱశ (2003) ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ࡅ࠻㛽⧘⚦⢩ߩ Gene
chip 䈮䉋䉎ㆮવሶ⊒⃻䊝䊆䉺䊥䊮䉫䇮ᣣᧄ䊧䊷䉱䊷ᱤቇળ✚ળ (ජ⪲⋵ⒷᲫᏒ)࡮ቇ૏ߩขᓧ⁁ᴫ(1) ᰞ੗㩷 ༀᐘ ඳ჻(ᱤቇ), F0F1-ATPase 䈍䉋䈶 COX-2 ㆮવሶ⊒⃻䈻䈱ૐ಴ജ䊧䊷䉱䊷ᾖ኿䈱ᓇ㗀,
2001 ᐕ 3 ᦬, ᣣᧄᄢቇ᧻ᚭᱤቇ⎇ⓥ⑼⺰ᢥඳ჻(2) ጊᧄ 㓷ਭඳ჻(ᱤቇ), 㛽⧘⚦⢩ߩㆮવሶ⊒⃻ߦਈ߃ࠆࡅ࠼ࡠࠠࠪ࡜ࠫࠞ࡞ಣℂࡈࠖࡉࡠࡀࠢ

࠴ࡦߣ࡟࡯ࠩ࡯ᾖ኿ߩᓇ㗀 2001 ᐕ 3 ᦬, ᣣᧄᄢቇ᧻ᚭᱤቇ⎇ⓥ⑼⺰ᢥඳ჻(3) ㊁᧛ ๺ม ඳ჻(ᱤቇ), ࡟࡯ࠩ࡯ᾖ኿ߦࠃࠆ㛽⧘⚦⢩ߩᏅಽൻㆮવሶࠢࡠ࡯࠾ࡦࠣߣᱤ⡺↱᧪✢⛽⧘⚦⢩ߩ IL-1E↥↢߳ߩᓇ㗀, 2001 ᐕ 4 ᦬, ᣣᧄᄢቇ᧻ᚭᱤቇ⎇ⓥ⑼⺰ᢥඳ჻(4) ᴡේ ਃ᣿ ඳ჻(ᱤቇ), ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߦࠃࠆ㛽⧘⚦⢩ߩ Macrophage Inhibitory Factor ㆮવሶ⊒⃻ߩჇᄢ, 2004 ᐕ 12 ᦬, ᣣᧄᄢቇ᧻ᚭᱤቇ⎇ⓥ⑼⺰ᢥඳ჻ቇ૏⺰ᢥⷐᣦ㧔ඳ჻㨯ᱤቇ㧕Effect of Low-Level Laser Irradiation on F0F1-ATPase and COX-2 Gene Expressions(F0F1-ATPase ߅ࠃ߮ COX-2 ㆮવሶ⊒⃻߳ߩૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߩᓇ㗀)ᣣᧄᄢቇ᧻ᚭᱤቇㇱ↢ൻቇᢎቶᰞ੗ ༀᐘ
㧔ᜰዉ㧦቟ቊሶቱశ ᢎ᝼㧕ⷐᣦ㧦ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߦഃ்ᴦ≹૞↪‫ޔ‬㛽᛬ᴦ≹ଦㅴ૞↪‫ޔ‬Ἳ∝ᛥ೙૞↪‫‛↢ߩߤߥޔ‬ቇ⊛ലᨐ߇޽ࠆ
ߣႎ๔ߐࠇߡ޿ࠆ‫ߩߘޔࠄ߇ߥߒ߆ߒޕ‬૞↪ᯏᐨߪᧂߛਇ᣿ߥὐ߇ᄙ޿‫࡯ࠩ࡯࡟ޕ‬ᴦ≮ࠍߐࠄߦផㅴߔࠆߚ
߼ߦߪ࡟࡯ࠩ࡯ᾖ኿ߩ↢‛ቇ⊛ലᨐߩᯏᐨࠍ⸃᣿ߔࠆᔅⷐ߇޽ࠅ‫࡯ࠩ࡯࡟ޔߦߢߔޔ‬ᾖ኿ߦࠃߞߡ㛽⧘⚦⢩ߢߩㆮવሶ⊒⃻߇ଦㅴߔࠆㆮવሶ࡜ࠗࡉ࡜࡝࡯ࠍ᭴▽ߒߡ޿ࠆ‫ޕ‬ㆮવሶ࡜ࠗࡉ࡜࡝࡯ਛߩㆮવሶࠢࡠ࡯ࡦߩ
৻ߟߢ޽ࠆ F0F1-ATPase subunit-b ߩㆮવሶ⊒⃻ߣ ATP ↥↢ߦਈ߃ࠆ࡟࡯ࠩ࡯ᾖ኿ߩᓇ㗀ߦߟ޿ߡᬌ⸛ߒߚ‫ޕ‬ ৻ᣇ‫ޔ‬ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿߇ᱤ๟∛ߩᱤ⡺Ἳ∝ࠍシᷫߔࠆߎߣ߇ႎ๔ߐࠇߡ޿ࠆ߇‫ߩߘޔ‬૞↪ᯏᐨߦߟ޿
ߡߪ᣿ࠄ߆ߦߥߞߡ޿ߥ޿‫ޕ‬Prostaglandin E2 (PGE2)ߪ‫ޔ‬㛽ๆ෼ଦㅴ࿃ሶ‫ޔ‬Ἳ∝ߩࡔ࠺ࠖࠛ࡯࠲࡯ߣߒߡ⍮ࠄࠇߡ߅ࠅ‫ޔ‬ᱤ๟∛ᖚ⠪ߩᱤ⡺ᶐ಴ᶧਛߩ PGE2 ㊂߇ஜᏱ⠪ߩ߽ߩߦᲧߴߡ᦭ᗧߦჇᄢߒߡ޿ࠆߎߣ‫ޔ‬ᱤ๟∛ᴦ≮ߦࠃߞߡᱤ⡺ᶐ಴ᶧਛߩ PGE2 ߇ૐਅߔࠆߎߣ߆ࠄᱤ๟∛ߩ⊒∝࡮ㅴዷߦ PGE2 ߇ᷓߊ㑐ਈߒߡ޿ࠆߎ
ߣ߇␜ໂߐࠇߡ޿ࠆ‫ߩ⩶⚦ޕ‬ౝᲥ⚛ߢ޽ࠆ࡝ࡐᄙ♧ (lipopolysaccharide; LPS) ߪ‫⿠ޔ‬Ἳ‛⾰‫ޔ‬㛽ๆ෼࿃ሶߣߒ
ߡᱤ๟∛ߩ∛ේ࿃ሶߣߥࠆ‫ޔߦߢߔޕ‬ᚑੱᕈᱤ๟Ἳߩ㑐ㅪ⩶ߢ޽ࠆߣ⠨߃ࠄࠇߡ޿ࠆ Campylobacter rectus ߩ
LPS ߇‫࠻ࡅޔ‬ᱤ⡺↱᧪✢⛽⧘⚦⢩ߩ PGE2 ↥↢ࠍଦㅴߔࠆߎߣ߇ႎ๔ߐࠇߡ޿ࠆ‫⎇ᧄߢߎߘޕ‬ⓥߢߪ‫ޔ‬ᱤ⡺↱᧪✢⛽⧘⚦⢩ߦ C. rectus ߩ LPS ࠍ૞↪ߐߖ‫ޔ‬ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߦࠃࠆ PGE2 ↥↢ߩᛥ೙ߦਈ߃ࠆᓇ㗀ࠍᬌ⸛ߒߚ‫⚿ߩߘޕ‬ᨐ‫ޔ‬એਅߩ⍮⷗ࠍᓧߚ‫ޕ‬
1. ࡑ࠙ࠬ㛽⧘⚦⢩ᩣ MC3T3-E1 ࠍ↪޿ߡ࡟࡯ࠩ࡯ᾖ኿ߦࠃߞߡ⊒⃻߇ଦㅴߔࠆ ㆮવሶߩᝌ౉ cDNA ߩႮၮ㈩೉ߪ࡜࠶࠻ߩ F0F1-ATPase subunit-b ㆮવሶߣ94.9㧑ߩࡎࡕࡠࠫ࡯ࠍ᦭ߒߡ޿ߚ‫ޔߚ߹ޕ‬Nothern-blot ಽᨆߩ⚿ᨐ߆ࠄ‫ޔ‬mRNA࡟ࡌ࡞߇࡟࡯ࠩ࡯ᾖ኿ߦࠃࠅჇᄢߔࠆߎߣ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߦࠃࠅ MC3T3-E1
⚦⢩ౝߩ ATP ㊂߇Ⴧᄢߔࠆߎߣ߇್᣿ߒߚ‫ޕ‬
2. ࡅ࠻ᱤ⡺↱᧪✢⛽⧘⚦⢩ߦᱤ๟∛ේ⩶ C. rectus LPS ࠍ૞↪ߐߖߚߣߎࠈ‫ޔ‬
PGE2 ↥↢߇Ⴧᄢߒߚ‫ޕ‬
3. ࡅ࠻ᱤ⡺↱᧪✢⛽⧘⚦⢩ߦᱤ๟∛ේ⩶ C. rectus LPS ࠍ૞↪ߐߖ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߒߚߣߎࠈ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ᤨ㑆ߦଐሽߒߡ PGE2 ↥↢㊂߇ᷫዋߒߚ‫ޕ‬
4. ࡟࡯ࠩ࡯ᾖ኿߇ㆮવሶ⊒⃻ߦਈ߃ࠆᓇ㗀ࠍᬌ⸛ߒߚ⚿ᨐ‫ޔ‬LPS ߢჇᄢߒߚ
 COX-2 mRNA ࡟ࡌ࡞߇࡟࡯ࠩ࡯ᾖ኿ߦࠃߞߡᷫዋߒߚ‫ޕ‬એ਄ߩ⚿ᨐ߆ࠄ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߩ㛽ᒻᚑଦㅴ૞↪‫ޔ‬᛫Ἳ∝૞↪‫ޔ‬ഃ்ᴦ≹૞↪ߥߤߩ↢‛ቇ⊛ലᨐߩᯏᐨߩ
⸃᣿ߩ৻ഥߣߒߡ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߪ‫ޔ‬㛽⧘⚦⢩ߩ ATP ↥↢⢻ࠍ F0F1-ATPase subunit-b ㆮવሶ⊒⃻ߩჇᄢࠍ੺
ߒߡଦㅴߔࠆߎߣ‫࠻ࡅޔ‬ᱤ⡺↱᧪✢⛽⧘⚦⢩ߩ PGE2 ↥↢⢻ࠍ COX-2 ㆮવሶ⊒⃻ߩᛥ೙ࠍ੺ߒߡᷫዋߐߖࠆ
ߎߣ߇᣿ࠄ߆ߣߥߞߚ‫ޕ‬ਥ⺰ᢥ㧦Inhibitory effect of low-level laser irradiation on LPS-stimulated prostaglandin E2 production andcyclooxygenase-2 in human gingival fibroblasts. Eur J Oral Sci, 108:29-34, 2000.
೽⺰ᢥ䋺Low level laser irradiation enhances expression of FoF1-ATPase subunit-b gene in osteoblastic cells. Laser
Therapy, 10: 107-116, 1998.

Effect of hydroxy radical treated fibronectin and laser irradiation on gene expressions in osteoblast㧔㛽⧘⚦⢩ߩㆮવሶ⊒⃻ߦਈ߃ࠆࡅ࠼ࡠࠠࠪ࡜ࠫࠞ࡞ಣℂࡈࠖࡉࡠࡀࠢ࠴ࡦߣ࡟࡯ࠩ࡯ᾖ኿ߩᓇ㗀㧕ᣣᧄᄢቇ᧻ᚭᱤቇㇱ↢ൻቇᢎቶጊᧄ 㓷ਭ
㧔ᜰዉ㧦቟ቊሶቱశ ᢎ᝼㧕ⷐᣦ㧦 㛽ᒻᚑᯏᐨߩ⸃᣿ߦะߌߡ‫ޔ‬㛽⧘⚦⢩ߩᖱႎવ㆐♽‫ޔ‬ㆮવሶ⊒⃻࡟ࡌ࡞ߢߩ⎇ⓥ߇ㅴዷߒߡ޿ࠆ‫ޕ‬㛽⚵❱ߩᯏ⢻⊒⃻ߦߪ㛽⧘⚦⢩ߩ⚦⢩ᄖࡑ࠻࡝࠶ࠢࠬࠍ੺ߔࠆᖱႎવ㆐♽߇㑐ਈߔࠆߎߣ߇᣿ࠄ߆ߦߐࠇ‫ޔ‬ࡑ࠻࡝࠶ࠢࠬ ࠲ࡦࡄࠢ⾰ߢ޽ࠆࡈࠖࡉࡠࡀࠢ࠴ࡦ߇㛽⧘⚦⢩ߩ⍹Ἧൻ⢻ߦ㊀ⷐߥᓎഀࠍᨐߚߒߡ޿ࠆߎߣ
߇⍮ࠄࠇߡ޿ࠆ‫ޕ‬ᒰᢎቶߢߪ‫ޔ‬㛽⧘⚦⢩ߩ⍹Ἧൻ⢻߇⠧ൻߦࠃߞߡૐਅߔࠆᯏᐨߩ⸃᣿ߩ৻ഥߣߒߡ‫ޔ‬㛽⧘⚦⢩ࠍࡅ࠼ࡠࠠࠪ࡜ࠫࠞ࡞ಣℂߒߚࡈࠖࡉࡠࡀࠢ࠴ࡦ਄ߢၭ㙃ߔࠆߎߣࠍ⹜ߺ‫ޔ‬㛽⚿▵ߩᒻᚑ߇⪺᣿ߦᛥ೙ߐࠇࠆߎߣࠍ⷗޿಴ߒߡ޿ࠆ‫࡞ࠞࠫ࡜ࠪࠠࡠ࠼ࡅߢߎߘޕ‬ಣℂߒߚࡈࠖࡉࡠࡀࠢ࠴ࡦ⚦⢩ၮ⾰߇㛽⧘⚦⢩ߩㆮવሶ⊒⃻ߦਈ߃ࠆᓇ㗀ߦߟ޿ߡᬌ⚝ߒߚ‫ޕ‬৻ᣇ‫ޔ‬ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߪ᛫Ἳ∝૞↪߿⚦⢩Ⴧᱺߩଦㅴലᨐߥߤ᭽‫‛↢ߥޘ‬ቇ⊛ലᨐࠍ᦭ߔࠆߎߣ߇⍮ࠄࠇߡ޿ࠆ‫ߦ․ޕ‬㛽⚵❱ߦ߅޿ߡߪ‫ޔ‬㛽⧘⚦⢩ߩಽൻ‫ޔ‬Ⴧᱺߩଦㅴ‫ޔ‬㛽ᒻᚑߩଦㅴߥߤ߇ᵈ⋡ߐࠇߡ޿ࠆ‫ޕ‬ߒ߆ߒߥ߇ࠄ‫ߩߘޔ‬૞↪ᯏᐨߦߪᧂߛਇ᣿ߥὐ߇ᄙ޿‫࡯ࠩ࡯࡟ޔߢߎߘޕ‬ᾖ኿߇㛽⧘⚦⢩ߦਈ߃ࠆᓇ㗀ࠍ↢ൻቇ⊛‫ޔ‬ಽሶ↢‛ቇ⊛ᚻᴺࠍ↪޿ߡ⸃᣿ߔࠆߎߣࠍ⋡⊛ߣߒߡ‫ޔ‬ᒰᢎቶߢߪߔߢߦ࡟࡯ࠩ࡯ᾖ኿ߦࠃߞߡ㛽⧘⚦⢩ߢㆮવሶ⊒⃻߇ଦㅴߐࠇࠆㆮવሶߩන㔌‫⸃ޔ‬ᨆࠍ⹜ߺߡ޿ࠆ‫ޕ‬ૐ಴ജ࡟࡯ࠩ࡯ (Ga-Al-As diode laser)ᾖ኿ߒߚࡑ࠙ࠬ㛽⧘⚦⢩᭽⚦⢩ᩣ(MC3T3-E1)ߩ cDNA ࡜ࠗࡉ࡜࡝࡯ࠍ૞⵾ߒ‫ޔ‬ߐࠄߦ࡟࡯ࠩ࡯ᾖ኿ߦࠃߞߡ
⊒⃻߇ଦㅴߒߚㆮવሶࠢࡠ࡯ࡦࠍ࡟࡯ࠩ࡯㕖ᾖ኿ mRNA ߣߩࠨࡉ࠻࡜࡚ࠢࠪࡦᴺߦࠃߞߡන㔌ߔࠆߎߣࠍ
⹜ߺߚ‫ޕ‬ㆮવሶࠢࡠ࡯ࡦ߆ࠄ♖⵾ߒߚࠗࡦࠨ࡯࠻ cDNA ߩႮၮ㈩೉ߩ৻ㇱࠍ⸃⺒ߒߚ⚿ᨐ‫ ࠬ࠙ࡑޔ‬MCM3
ㆮવሶߣ㜞޿⋧หᕈࠍ߽ߟࠢࡠ࡯ࡦ(MCL-140)߇ᓧࠄࠇߚ‫⎇ᧄޕ‬ⓥߢߪ MCL-140 ࠢࡠ࡯ࡦߦߟ޿ߡႮၮ㈩೉
⸃ᨆ‫࠻࠶ࡠࡉࡦࠩ࡯ࡁޔ‬ಽᨆࠍⴕ޿‫࡯ࠩ࡯࡟ߦࠄߐޔ‬ᾖ኿ߩ DNA วᚑߦਈ߃ࠆᓇ㗀ߦߟ޿ߡᬌ⸛ߒ‫ޔ‬એਅߩ⚿ᨐࠍᓧߚ‫ޕ‬
1. ࡈࠖࡉࡠࡀࠢ࠴ࡦߩࡅ࠼ࡠࠠࠪ࡜ࠫࠞ࡞ಣℂߦࠃߞߡ㛽⧘⚦⢩᭽⚦⢩ MC3T3-E1 ߩࠕ࡞ࠞ࡝ࡎࠬࡈࠔ
࠲࡯࠯‫ޔ‬I ဳࠦ࡜࡯ࠥࡦㆮવሶߩ mRNA ࡟ ࡌ࡞߇ኻᾖ⟲ߦᲧߴߡૐਅߒߚ‫ޕ‬
2. ࡟࡯ࠩ࡯ᾖ኿ MC3T3-E1 ߩࠨࡉ࠻࡜࡚ࠢࠪࡦᴺ࡜ࠗࡉ࡜࡝࡯߆ࠄᓧߚ  MCL-140 ࠢࡠ࡯ࡦ cDNA ࠗࡦࠨ࡯࠻ߩႮၮ㈩೉ࠍ⸃⺒ߒ‫࡯ࠫࡠࡕࡎޔ‬ᬌ⚝ࠍⴕߞߚߣߎࠈ‫ޔ‬ᣢ⍮ߩࡑ࠙ࠬ MCM3 ㆮવሶߣႮၮ㈩೉ߢ 99.6㧑ߩ⋧หᕈࠍ⹺߼ߚ‫ޕ‬
3. ࡟࡯ࠩ࡯ᾖ኿߅ࠃ߮㕖ᾖ኿ߩ MC3T3-E1 ⚦⢩߆ࠄ RNA ↹ಽࠍ⺞⵾ߒ‫ޔ‬
cDNA ࠗࡦࠨ࡯࠻߅᡼኿ᕈ DNA ࡊࡠ࡯ࡉࠍ↪޿ߡࡁ࡯ࠩࡦࡉࡠ࠶࠻ಽᨆ
ߒߚ⚿ᨐ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿⟲ߢᾖ኿ᓟ 6 ᤨ㑆ᓟߦ࡟࡯ࠩ࡯㕖ᾖ኿⟲ߦᲧセߒ
ߡ mRNA ࡟ࡌ࡞ߩჇᄢ߇⹺߼ࠄࠇߚ‫ޕ‬
4. ࡟࡯ࠩ࡯ᾖ኿ᓟMC3T3-E1 ⚦⢩ߦ߅ߌࠆDNA วᚑ⢻ࠍ᡼኿ᕈ࠴ࡒࠫࡦߩขࠅㄟߺ㊂ߦࠃࠅᬌ⸛ߒߚ⚿ᨐ‫࡯ࠩ࡯࡟ޔ‬㕖ᾖ኿⟲ߦᲧセߒߡขࠅㄟߺ㊂ߩჇടࠍ⹺߼ߚ‫ޕ‬ MCM3 ㆮવሶߪ‫⌀ޔ‬ᩭ⚦⢩ߩ⚦⢩ಽⵚᤨߦ DNA ⶄ⵾߇⚦⢩๟ᦼߩ S ᦼߦߚߛ৻ᐲߛߌ⿠ߎࠆߎߣࠍ଻⸽
ߔࠆᱜߩ೙ᓮ࿃ሶ‫ࠬࡦ࠮ࠗ࡜ࠆࠁࠊ޿ޔ‬࿃ሶߩ৻ຬߣߒߡᵈ⋡ߐࠇ‫⌀ޔ‬ᩭ⚦⢩ߩ DNA ⶄ⵾ߦᔅ㗇ߢ޽ࠆߎߣ߇᣿ࠄ߆ߦߥߞߡ޿ࠆ‫⎇ᧄޕ‬ⓥߩ⚿ᨐ߆ࠄ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߪ‫ޔ‬MCM3 ㆮવሶߩㆮવሶ⊒⃻ࠍଦㅴߔࠆߎߣ
ߢ⚦⢩๟ᦼࠍㅴⴕߐߖ‫⚦ޔ‬⢩Ⴧᱺߦ㑐ਈߔࠆߎߣ߇␜ໂߐࠇߚ‫ޕ‬ਥ⺰ᢥ㧦Stimulation of MCM3 gene expression in

osteoblast by low level laser irradiation. Lasers Med Sci, 16:

213-217, 2001.
ෳ⠨⺰ᢥ㧦H2O2-derived free radicals treated fibronectin substratum reduces the bone nodule formation of rat calvarial
osteoblast. Mech Ageing Dev, 98: 113-125, 1997.

Subtractive Gene Cloning from Osteoblast and Effect of IL-1E Production in Gingival Fibroblasts by Laser
Irradiation(࡟࡯ࠩ࡯ᾖ኿ߦࠃࠆ㛽⧘⚦⢩ߩᏅಽൻㆮવሶࠢࡠ࡯࠾ࡦࠣߣᱤ⡺↱᧪✢⛽⧘⚦⢩ߩ IL-1Eҏ↥↢߳ߩᓇ㗀)ᣣᧄᄢቇ᧻ᚭᱤቇㇱ↢ൻቇᢎቶ㊁᧛ ๺ม
㧔ᜰዉ㧦቟ቊሶቱశ ᢎ᝼㧕ⷐᣦ㧦ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿߇ഃ்߿㔍ᴦᕈẩ≌ߦᴦ≹ലᨐ߇޽ࠆߣ⸒෸ߐࠇߡએ᧪‫ޔ‬Ἳ∝ᛥ೙‫ޔ‬−∩ᷫዋ‫ޔ‬ഃ்ᴦ≹ଦㅴ‫ޔ‬㛽᛬ᴦ≹ଦㅴߥߤᐢ▸ߥ⥃ᐥലᨐ߇ႎ๔ߐࠇߡ޿ࠆ‫৻ࠄ߇ߥߒ߆ߒޕ‬ᣇߢߪ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߩലᨐߦߟ޿ߡᔃℂ⊛ߥࡊ࡜࠮ࡏ࡯ലᨐ߇ᄢ߈޿ߢ޽ࠈ߁ߣߔࠆᗧ⷗߿‫‛↢ޔ‬ቇ⊛ലᨐߪ᷷ᐲ਄᣹ലᨐߦࠃ
ࠆනߥࠆⴊᶧᓴⅣߩଦㅴലᨐߢ޽ࠈ߁ߣߔࠆ⼏⺰߽ߐࠇߡ޿ࠆ‫ߥ߁ࠃߩߎޕ‬⢛᥊߆ࠄ࡟࡯ࠩ࡯ᾖ኿ߩ↢‛ቇ⊛ലᨐߩ૞↪ᯏᐨߩ⸃᣿ߪਇචಽߢ޽ࠅ‫ޔ‬ᱤ⑼කቇ㗔ၞߦ߽Ⓧᭂ⊛ߥᔕ↪߇ᦼᓙߐࠇߡ޿ࠆߥ߆ߢ‫ࠩ࡯࡟ޔ‬࡯ක≮ࠍߐࠄߦផㅴߔࠆߚ߼ߦߪ‫↪᦭ޔ‬ᕈߩ㜞޿࡟࡯ࠩ࡯ᾖ኿ߩᯏ⒳‫ޔ‬ᾖ኿ᴺࠍ㐿⊒ߔࠆߣߣ߽ߦ‫‛↢ޔ‬ቇ⊛ലᨐࠍታ⸽⑼ቇ⊛ߦ⸃᣿ߒߡ޿ߊᔅⷐ߇޽ࠆߣᕁࠊࠇࠆ‫ޕ‬ ᧄ⎇ⓥߢߪ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߩ↢‛ቇ⊛ലᨐࠍታ⸽⑼ቇ⊛ߦ⸽᣿ߒ‫⸃ࠍࡓ࠭࠾ࠞࡔߩߘޔ‬᣿ߔࠆߚ߼ߦ‫࡟ޔ‬࡯ࠩ࡯ᾖ኿ߦࠃߞߡ㛽⧘⚦⢩ߢߩㆮવሶ⊒⃻߇ଦㅴߔࠆㆮવሶࠍត⚝ߔࠆߚ߼ߦᏅಽൻㆮવሶ࡜ࠗࡉ࡜࡝࡯
ࠍ᭴▽ߒߚ‫⚿ߩߘޕ‬ᨐ‫ࠣࡦࠪࡦ࠮ࠗ࡜ޔ⾰ࠢࡄࡦ࠲ࠕ࡝࠼ࡦࠦ࠻ࡒޔ‬࿃ሶ‫ޔ‬ォ౮࿃ሶߥߤߩㆮવሶࠢࡠ࡯ࡦ
߇߃ࠄࠇߚ‫ޕ‬ ৻ᣇ‫ޔ‬ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿߇ᱤ๟∛ߩᱤ⡺Ἳ∝ࠍシᷫߔࠆߎߣ߇ႎ๔ߐࠇߡ޿ࠆ߇‫ߩߘޔ‬૞↪ᯏᐨߦߟ޿
ߡߪ᣿ࠄ߆ߦߥߞߡ޿ߥ޿‫ޕ‬IL-1Eߪ‫ޔ‬㛽ๆ෼ଦㅴ࿃ሶ‫ޔ‬Ἳ∝ߩࡔ࠺ࠖࠛ࡯࠲࡯ߣߒߡ⍮ࠄࠇߡ߅ࠅ‫ޔ‬ᱤ๟∛ᖚ⠪ߩᱤ⡺ᶐ಴ᶧਛߩ IL-1E㊂߇ஜᏱ⠪ߦᲧߴߡ᦭ᗧߦჇᄢߒߡ޿ࠆߎߣ߆ࠄᱤ๟∛ߩ⊒∝࡮ㅴዷߦᷓߊ㑐ਈߒߡ޿ࠆߎߣ߇␜ໂߐࠇߡ޿ࠆ‫ߩ⩶⚦ޕ‬ౝᲥ⚛ߢ޽ࠆ࡝ࡐᄙ♧ (lipopolysaccharide; LPS) ߪ‫⿠ޔ‬Ἳ‛⾰‫ޔ‬㛽ๆ෼࿃ሶߣߒߡᱤ๟∛ߩ∛ේ࿃ሶߣߥࠆ‫ޔߦߢߔޕ‬ᚑੱᕈᱤ๟Ἳߩ㑐ㅪ⩶ Campylobacter rectus ߩ LPS ߇‫ࡅޔ‬࠻ᱤ⡺↱᧪✢⛽⧘⚦⢩ߩ IL-1E↥↢ࠍଦㅴߔࠆߎߣ߇ႎ๔ߐࠇߡ޿ࠆ‫⎇ᧄߢߎߘޕ‬ⓥߢߪ‫ޔ‬ᱤ⡺↱᧪✢⛽⧘⚦⢩ߦ C. rectus ߩ LPS ࠍ૞↪ߐߖ‫ޔ‬ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߦࠃࠆ IL-1E↥↢ߩᛥ೙ߦਈ߃ࠆᓇ㗀ࠍᬌ⸛ߒߚ‫ޕ‬ߘߩ⚿ᨐ‫ޔ‬C. rectus LPS ࠍ૞↪ߐߖߚࡅ࠻ᱤ⡺↱᧪✢⛽⧘⚦⢩ߩၭ㙃ᶧਛ IL-1E㊂ ߇Ⴧᄢߒߚ‫࡟ޔߡߒߘޕ‬࡯ࠩ࡯ᾖ኿ᤨ㑆ߦଐሽߒߡߎߩ IL-1E㊂߇ᷫዋߒߚ‫࠻ࡅޔߦࠄߐޕ‬ᱤ⡺↱᧪✢⛽⧘⚦⢩ߩ࡟࡯ࠩ࡯ᾖ኿ߦࠃ
ࠆ LPS ଐሽᕈ IL-1E↥↢㊂ߩౣ⃻ᕈࠍᬌ⸛ߒߚߣߎࠈ 5 ੱߩ࠼࠽࡯߆ࠄᓧࠄࠇߚᱤ⡺↱᧪✢⛽⧘⚦⢩ߢห᭽ߩ⚿ᨐ߇⷗ࠄࠇߚ‫࡯ࠩ࡯࡟ޔߚ߹ޕ‬ᾖ኿߇ㆮવሶ⊒⃻ߦਈ߃ࠆᓇ㗀ࠍᬌ⸛ߒߚ⚿ᨐ‫ޔ‬LPS ߢჇᄢߒߚ IL-1E
mRNA ࡟ࡌ࡞߇࡟࡯ࠩ࡯ᾖ኿ߦࠃߞߡᷫዋߒߚ‫ޕ‬એ਄ߩ⚿ᨐ߆ࠄ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߩ㛽ᒻᚑଦㅴ૞↪‫ޔ‬᛫Ἳ∝૞↪‫ޔ‬ഃ்ᴦ≹૞↪ߥߤߩ↢‛ቇ⊛ലᨐߩᯏᐨ
ߣߒߡ‫࡯ࠩ࡯࡟ޔ‬ᾖ኿ߪ‫ޔ‬㛽⧘⚦⢩ߩㆮવሶ⊒⃻࡟ࡌ࡞ࠍᄌൻߐߖࠆߎߣ‫࠻ࡅޔ‬ᱤ⡺↱᧪✢⛽⧘⚦⢩ߩ IL-1E↥↢⢻ࠍㆮવሶ⊒⃻ߩᛥ೙ࠍ੺ߒߡᷫዋߐߖࠆߎߣ߇␜ໂߐࠇߚ‫ޕ‬ਥ⺰ᢥ㧦Inhibition of interleukin 1E production expression in gingival fibroblasts by low-energy laser irradiation. Lasers
Med Sci,16: 218-223. 2001.
ෳ⠨⺰ᢥ㧦Construction of subtracted osteoblast cDNA library with laser-irradiation-enhanced transcription. Laser
Therapy, 9: 107-114, 1997.

Enhancement of Macrophage Inhibitory Factor Gene Expression in Osteoblasts by Low Level Laser Irradiation㧔ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߦࠃࠆ㛽⧘⚦⢩ߩ Macrophage Inhibitory Factor ㆮવሶ⊒⃻ߩჇᄢ㧕ᣣᧄᄢቇ᧻ᚭᱤቇㇱ↢ൻቇᢎቶᴡේ ਃ᣿
㧔ᜰዉ㧦቟ቊሶቱశ ᢎ᝼㧕ⷐᣦ㧦ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߪ᛫Ἳ∝૞↪߿⚦⢩Ⴧᱺߩଦㅴലᨐߥߤ᭽‫‛↢ߥޘ‬ቇ⊛ലᨐࠍ᦭ߔࠆߎߣ߇⍮ࠄࠇߡ޿ࠆ‫ߦ․ޕ‬㛽⚵❱ߦ߅޿ߡߪ‫ޔ‬㛽⧘⚦⢩ߩಽൻ࡮Ⴧᱺߩଦㅴ‫ޔ‬㛽ᒻᚑߩଦㅴ૞↪߇ᵈ⋡ߐࠇߡ޿ࠆ‫ޕ‬ㄭᐕ‫ޔ‬ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߩ㛽ᒻᚑଦㅴ૞↪ߦᵈ⋡ߒߡญ⣧ࠗࡦࡊ࡜ࡦ࠻≮ᴺ߳ߩ࡟࡯ࠩ࡯ᴦ≮ߩᔕ↪ߦ⥝๧߇߽ߚࠇߡ޿ࠆ‫ޕ‬ߒ߆ߒߥ߇ࠄ࡟࡯ࠩ࡯ᾖ኿ߦ߅ߌࠆ㛽ᒻᚑ⢻ߩଦㅴലᨐߩᯏᐨߦߟ޿ߡߪਇ᣿ߥὐ߇ᄙ޿‫ޕ‬ߣߊߦ⚦⢩↢‛ቇ⊛ߥಽሶ࡟ࡌ࡞ߢߩ⸃᣿ߪㅴࠎߢ޿ߥ޿‫⪺ޕ‬⠪ࠄߩ⎇ⓥቶߢߪ‫ࠬ࠙ࡑޔ‬㛽⧘⚦⢩᭽ᩣ
MC3T3-E1 ⚦⢩߳ߩ࡟࡯ࠩ࡯ᾖ኿ߦࠃߞߡㆮવሶ⊒⃻߇ଦㅴߔࠆㆮવሶࠍcDNA ࡑࠗࠢࡠࠕ࡟ࠗࠍᔕ↪ߒߡ⊒⃻ᄌേㆮવሶߩ⸃ᨆࠍ⹜ߺߡ޿ࠆ‫ޔߚ߹ޕ‬㕖ᾖ኿ߩ mRNA ࠍ↪޿ߡᏅಽൻߒߚㆮવሶ࡜ࠗࡉ࡜࡝࡯ࠍ᭴▽ߒߡ‫ޔ‬ಽሶ↢‛ቇ⊛ߦ࡟࡯ࠩ࡯ᾖ኿ߦࠃߞߡ⊒⃻߇Ⴧᄢߔࠆㆮવሶߩ⸃᣿ࠍ⹜ߺߡ޿ࠆ‫ޕ‬ ᧄ⎇ⓥߢߪ‫ޔ‬Ꮕಽൻㆮવሶᴺߦࠃࠅ annexin III ㆮવሶࠍ‫ޔߚ߹ޔ‬cDNA ࡑࠗࠢࡠࠕ࡟ࠗᴺߦࠃࠅ osteogl㨥
cin ㆮવሶ߇ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߦࠃߞߡ mRNA ࡟ࡌ࡞߇Ⴧᄢߔࠆߎߣࠍ⷗಴ߒ‫ޔߦࠄߐޔ‬RT-PCR, real-time
PCR ᴺࠍ↪޿ߡ⏕⹺ߒߚ‫ޕ‬Annexin III ߪ‫⚦⧘࡞ࡔ࠽ࠛޔ‬⢩߿⽎‎⧘⚦⢩ߦ⷗޿ߛߐࠇ‫⚦ޔ‬⢩ࠞ࡞ࠪ࠙ࡓߩ⺞▵ߦ㑐ਈߔࠆߣ޿ࠊࠇߡ޿ࠆ‫ޔߚ߹ޕ‬osteogl㨥cin ߪᓥ᧪‫ޔ‬㛽⺃ዉ࿃ሶߣߒߡ♖⵾ߐࠇߚᮡຠߩ᭴ᚑᚑಽߢ޽
ࠆࡊࡠ࠹ࠝࠣ࡝ࠞߢ޽ࠆ‫ޕ‬ ߹ߚ‫⎇ᧄޔ‬ⓥߢߪᣂߚߦᏅಽൻㆮવሶ࡜ࠗࡉ࡜࡝࡯߆ࠄ MCL-176 ㆮવሶࠢࡠ࡯ࡦࠍㆬ߮‫⚵ޔ‬឵߃ㆮવሶ
ᝌ౉ DNA ߩႮၮ㈩೉ࠍ⸃⺒ߒ‫ޔ‬NCBI DNA ࠺࡯࠲ࡌ࡯ࠬࠍ೑↪ߒߡႮၮ㈩೉ߩࡎࡕࡠࠫ࡯⸃ᨆࠍⴕߞߚ‫ޕ‬ߘߩ⚿ᨐ‫ޔ‬MCL-176 ㆮવሶߪࡑ࠙ࠬߩ macrophage inhibitory factor (MIF) ㆮવሶ⟲ߣ 99% એ਄ߩ㜞޿ࡎࡕࡠࠫ࡯ࠍ߽ߟߎߣ߇᣿ࠄ߆ߦߥߞߚ‫ޕ‬ᰴ޿ߢ࡟࡯ࠩ࡯ᾖ኿‫ޔ‬㕖࡟࡯ࠩ࡯ᾖ኿ߩ MC3T3-E1 ⚦⢩߆ࠄ mRNA ࠍ࿁෼ߒߡ cDNA ࠍวᚑߒ‫ޔ‬reverse transcription-polymerase chain reaction (RT-PCR) ㆮવሶჇ᏷ᴺߢಽᨆߒߚߣ
ߎࠈ‫ޔ‬࡟࡯ࠩ࡯ᾖ኿ᓟ‫ޔ‬㧢㧘㧞㧠 ᤨ㑆ߢMIF mRNA ࡟ࡌ࡞߇Ⴧᄢߔࠆߎߣࠍ⷗޿ߛߒߚ‫ޕ‬ߐࠄߦreal- time PCRᴺࠍ↪޿ߡ⏕⹺ߒߚߣߎࠈ‫ޔ‬ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߪ㛽⧘⚦⢩ߩ MIF ㆮવሶ mRNA ߩ⊒⃻ࠍჇᄢߐߖࠆߎߣ
߇⏕⹺ߐࠇߚ‫ޕ‬MIF ߪ‫ޔ‬ᓥ᧪‫ޔ‬⒳‫ޔߢࡦࠗࠞ࠻ࠗࠨࠆࠇߐ↢↥ߢ❱⚵ߩޘ‬Ἳ∝ࡊࡠ࠮ࠬߦ㑐ਈߔࠆߎߣ߇⍮ࠄࠇߡ޿ߚ߇‫ᦨޔ‬ㄭ‫ޔ‬㛽⧘⚦⢩ߦ߽↥↢ߐࠇߡ߅ࠅ‫ޔ‬㛽⧘⚦⢩ߩჇᱺ߿㛽ᡷㅧࠍ⺞▵ߔࠆᯏ⢻ࠍ߽ߟߎߣ߇
␜ໂߐࠇߡ޿ࠆ‫ޕ‬ ᧄ⎇ⓥߩ⚿ᨐ‫ޔ‬ૐ಴ജ࡟࡯ࠩ࡯ᾖ኿ߦࠃߞߡ㛽⧘⚦⢩ߩ annexin III‫ޔ‬osteo- gl㨥cin‫ޔ‬MIF ㆮવሶߩ⊒⃻߇ଦㅴߐࠇࠆߎߣ߇᣿ࠄ߆ߦߥࠅ‫ߩࠄࠇߎޔ‬ㆮવሶ↥‛߇࡟࡯ࠩ࡯ᾖ኿ߦࠃࠆ㛽ᒻᚑଦㅴࡔࠞ࠾࠭ࡓߦ㑐ਈߔࠆน⢻ᕈ߇␜ໂߐࠇࠆ‫ޕ‬ਥ⺰ᢥ㧦Enhanced Gene Expression by Low-Level Laser Irradiation in Osteoblast -Identification of Annexin III Gene by
Subtractive Gene Cloning. J Jap Soc. Oral Implantol, 17: 3-12, 2004.
ෳ⠨⺰ᢥ㧦 Enhanced Gene Expression by Low-Level Laser Irradiation in Osteoblast - Identification od annexin III
Gene by Subtractive Gene cloning-”, J Jap Soc. Oral Implantol, 15:323-329, 2002
Effect of Low-Level Laser Irradiation onOsteoglycin Gene Expression in Osteoblasts” Lasers in Medical Science
18:78-82, 2003.

࿖㓙ળ⼏ߩ੍Ⓜ㓸
Annual Meeting of International Socoety for Laser in Dentistry:Laser in Dentistry,: Revolution of Dental Treatment in the
new millennium
Genome Science–Based Gene Expression Monitoring in Osteoblasts Altered by Low-Level Laser Irradiation
Y. Abiko, K. Hiratsuka, *M. Ohta, *K. Ide and *H. Sasahara.
Department of Biochemistry and *Oral Diagnostics, and Research Institute of Oral Science, Nihon University School of
Dentistry at Matsudo, Chiba, Japan.
Although the acceleration of bone regeneration by low-level laser irradiation (LLLI) has been reported, the molecular
based mechanisms are not well elucidated. Advances in the technology for assaying transcription levels, in a highly
parallel fashion coupled with the completion of genome projects, make possible a complete description of gene regulatory
systems. The transcription profile analysis such as gene subtraction and DNA microarray technology make possible todiscover large number of genes altered their transcription levels by LLLI.
In this study, we have focussed on the characterization of genes altered in osteoblast cells by LLLI and attempted toelucidate the mechanism of biostimulatory effects on bone regeneration using the subtractive gene cloning and cDNA
microarray-based expression monitoring system. Subtractive cDNA library of MC3T3-E1, a clonal osteoblast cell line,
was constructed using a stepwise subtraction procedure. Nucleotide sequencing of each gene clone was carried out andassessed by homology search in DNA databases. To find transcriptional profiling, we also examined mRNA levels of
3,800 genes using the gene expression cDNA microarray (AtlasTM Glass Mouse 3.8. Clonetech). Total RNAs wereisolated and synthesized to cDNAs, and then labeled with fluorescence dye cy3 or cy5. After hybridization with themicroarray, signals of fluorescently-labeled cDNAs were followed by computer analysis to derive relative changes in
expression level of the genes.
Many genes altered their expression levels by LLLI were identified including ATP synthesis, DNA replication,transcription and translation, growth factor, and other unknown function genes including ESTs. These findings suggest that
LLLI may demonstrate biostimulatory effects on osteoblasts through expression of many gene, and cDNA subtraction andDNA microarray technology will provide unprecedented access to elucidate the mechanism of bone regeneration
stimulated by LLLI.

Effect of Low-Level Laser Irradiation on IL-8 Production in Synovial Cells from Human Temporomandibular
Joint
M. Ohta1,4, K, K. Ide1,4, N. Ogura3,4, M. Tobe3, H. Sakamaki3,4, H. Sasahara1,4 and Y. Abiko2,4,Department of 1Oral Diagnostics, 2Biochemistry, 3Oral Surgery, and 4Research Institute of Oral Science, Nihon University
School of Dentistry at Matsudo, Chiba, Japan
Biostimulatory effects of low-level laser irradiation (LLLI), such as anti-inflammation ad relieving pain against
temporomandibular joint (TMJ) disorders, have been reported. However, the molecular based mechanisms are not
elucidated yet. Synovial cells are believed to play pathological roles in the development and continuation of inflammation
via the release of proteases and oxidative products. Infiltrating cells recruited from blood are mediated by chemotactic
factors released by activated synovial cells. IL-8, a member of a chemokine superfamily, has been found in synovial fluid
as well as IL-1E from patients with TMJ synovitis.

The purpose of this study is examined the effect of LLLI on the IL-8 production stimulated by IL-1E in humansynovial fibroblasts. The cells were isolated from TMJ synovial tissues and primary cultured using outgrowth method. The
confluent-stage cells were treated with IL-1Eѽҏas the same time, LLLI (Linear polarized near infra-red laser; Super Lizer,
Tokyo Iken; 645-1,050 nm range) was treated to the cells. The amounts of IL-8 in conditioned medium were measured by
ELISA kit. IL-1E induced IL-8 production from synovial fibroblasts in a time- and dose-dependent manner. LLLI
significantly reduced IL-8 production in early time. The LLLI did not destroy IL-1Eҏand IL-8 directly in the experimental
condition. These findings suggest that LLLI may have anti-inflammatory effect on TMJ disorder through the reduction of
IL-8 production.
This study was supported in part by A Grants from the Ministry of Education, Culture, Sports, Science, and Technologyof Japan to promote Multidisciplinary Research Projects.