リン代謝と口腔疾患

Phosphate homeostasis and oral diseases.

　リンの代謝調節においては，主として骨細胞により産生されるfibroblast growth factor 23（FGF23）が中心的な役割を担い，腎臓におけるリン酸再吸収やビタミンＤ活性化を制御する。FGF23およびその産生制御に関わるPHEX，DMP1，FAM20Cなどの変異は遺伝性低リン血症の原因となる。これらの疾患においてはしばしば歯科症状を伴うが，低リン血症やビタミンＤの作用不全による象牙質の石灰化障害に加え，PHEX機能喪失に伴うASARMペプチドの蓄積やDMP1機能喪失に伴うDSPP発現低下など，責任分子特異的な機序の関与も推察されている。

　FGF23 produced mainly by osteocytes plays a central role in phosphate homeostasis by increasing the renal phosphate excretion and suppressing the vitamin D activation. Mutations in FGF23 and its regulatory molecules such as PHEX, DMP1, and FAM20C have been shown to be responsible for hereditary hypophosphatemic diseases. Patients and animal models of these hypophosphatemic conditions often manifest dental defects, whose etiology may include hypophosphatemia and impaired vitamin D action. In addition, the mechanisms specific to each responsible gene such as accumulated ASARM peptides in PHEX deficiency and the reduced DSPP expression in DMP1 deficiency are also involved in the pathogenesis of these dental problems.