The receptor activator of nuclear factor-B ligand-mediated osteoclastogenic pathway is elevated in amelogenin-null mice
The receptor activator of nuclear factor-B ligand-mediated osteoclastogenic pathway is elevated in amelogenin-null mice
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DOI：
10.1074/jbc.m306284200
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发表时间：
2003-09-12
影响因子：
4.8
通讯作者：
Kulkarni, AB
中科院分区：
文献类型：
--
作者：
Hatakeyama, J;Sreenath, T;Kulkarni, AB
釉原蛋白是发育中的牙釉质的主要成分，主要参与牙釉质的形成。尽管釉原蛋白也与牙骨质生成有关，但其确切的空间表达模式和分子作用尚不清楚。在此，我们首次报道了釉原蛋白的两种可变剪接形式，M180和富含亮氨酸的釉原蛋白肽（LRAP）在小鼠牙根的牙周区域的表达。M180和LRAP mRNA表达缺失与在釉原蛋白缺失小鼠中观察到的牙骨质缺陷相关。牙骨质缺陷的特征是多核细胞、破骨细胞和牙骨质小体增多。这些缺陷与核因子 - κB受体活化因子配体（RANKL）表达增加有关，RANKL是破骨细胞生成的关键调节因子。这些发现表明，釉原蛋白剪接变体M180和LRAP对于防止牙骨质异常吸收至关重要。
Amelogenins, major components of developing enamel, are predominantly involved in the formation of tooth enamel. Although amelogenins are also implicated in cementogenesis, their precise spatial expression pattern and molecular role are not clearly understood. Here, we report for the first time the expression of two alternate splice forms of amelogenins, M180 and the leucine-rich amelogenin peptide ( LRAP), in the periodontal region of mouse tooth roots. Lack of M180 and LRAP mRNA expression correlated with cementum defects observed in the amelogenin-null mice. The cementum defects were characterized by an increased presence of multinucleated cells, osteoclasts, and cementicles. These defects were associated with an increased expression of the receptor activator of the nuclear factor-kappaB ligand ( RANKL), a critical regulator of osteoclastogenesis. These findings indicate that the amelogenin splice variants, M180 and LRAP, are critical in preventing abnormal resorption of cementum.