副交感神経によるα7ニコチン性アセチルコリンレセプター(α7nAchR)を介した骨調節機構の解明を行った。α7nAchRは, 副交感神経系を介しマクロファージからのTNFαを抑制し, 骨芽細胞でのOPG, RANKLを制御することで破骨細胞の活性を正に制御し骨量低下に導く調節系に関わること, また, ニコチンはこの系を活性化することが示された。今回の解析により, 副交感神経系による骨恒常性制御のメカニズムと, 喫煙による作用物質であるニコチンが骨に及ぼす作用機序を新たに明らかにすることができた。
The nicotinic receptor α7nAchR reportedly regulates vagal nerve targets in brain and cardiac tissues, and the parasympathetic nervous system; however, ite roles in bone metabolism were remained to be elucidated. Moreover, smoking is known as a risk of osteoporosis development, however, the mechanisms underlying have not been clarified. Our study revealed that α7nAchR suppressed TNFαexpression in macrophages, decreased osteoprotegerin/RANKL ratio via the parasympathetic nervous system and upregulated osteoclastogenesis, resulting in loss of bone mass. Nicotine, the ligand of α7nAchR, activated the system. We now clarified a novel mechanism underlying controlling bone metabolism by the parasympathetic nervous system, and how nicotine, a main bioactive substance taken by smoking, affected bone.
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