Haruyama Naoto, Hatakeyama Junko, Moriyama Keiji, Kulkarni Ashok B
GCOE Program, International Research Center for Molecular Science in Tooth and Bone Diseases Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan ; Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
J Oral Biosci. 2011 Aug 1;53(3):257-266.
Amelogenins are the most abundant extracellular matrix proteins secreted by ameloblasts during tooth development and are important for enamel formation. Recently, amelogenins have been detected not only in ameloblasts, which are differentiated from the epithelial cell lineage, but also in other tissues, including mesenchymal tissues at low levels, suggesting that amelogenins possess other functions in these tissues. The therapeutic application of an enamel matrix derivative rich in amelogenins resulted in the regeneration of cementum, alveolar bone, and periodontal ligament (PDL) in the treatment of experimental or human periodontitis, indicating the attractive potential of amelogenin in hard tissue formation. In addition, a full-length amelogenin (M180) and leucine-rich amelogenin peptide (LRAP) regulate cementoblast/PDL cell proliferation and migration . Interestingly, amelogenin null mice show increased osteoclastogenesis and root resorption in periodontal tissues. Recombinant amelogenin proteins suppress osteoclastogenesis and , suggesting that amelogenin is involved in preventing idiopathic root resorption. Amelogenins are implicated in tissue-specific epithelial-mesenchymal or mesenchymal-mesenchymal signaling; however, the precise molecular mechanism has not been characterized. In this review, we first discuss the emerging evidence for the additional roles of M180 and LRAP as signaling molecules in mesenchymal cells. Next, we show the results of a yeast two-hybrid assay aimed at identifying protein-binding partners for LRAP. We believe that gaining further insights into the signaling pathway modulated by the multifunctional amelogenin proteins will lead to the development of new therapeutic approaches for treating dental diseases and disorders.
釉原蛋白是成釉细胞在牙齿发育过程中分泌的最丰富的细胞外基质蛋白，对牙釉质形成至关重要。最近，不仅在源自上皮细胞谱系的成釉细胞中检测到了釉原蛋白，在包括间充质组织在内的其他组织中也检测到了低水平的釉原蛋白，这表明釉原蛋白在这些组织中具有其他功能。富含釉原蛋白的牙釉质基质衍生物在治疗实验性或人类牙周炎时可促使牙骨质、牙槽骨和牙周韧带再生，这表明釉原蛋白在硬组织形成方面具有诱人的潜力。此外，全长釉原蛋白（M180）和富含亮氨酸的釉原蛋白肽（LRAP）可调节成牙骨质细胞/牙周韧带细胞的增殖和迁移。有趣的是，釉原蛋白基因敲除小鼠的牙周组织中破骨细胞生成增加且牙根吸收增多。重组釉原蛋白可抑制破骨细胞生成，这表明釉原蛋白参与预防特发性牙根吸收。釉原蛋白与组织特异性上皮-间充质或间充质-间充质信号传导有关；然而，其确切的分子机制尚未明确。在本综述中，我们首先讨论M180和LRAP作为间充质细胞中信号分子的新作用的新证据。接下来，我们展示了旨在鉴定LRAP蛋白结合伙伴的酵母双杂交试验结果。我们相信，进一步深入了解由多功能釉原蛋白调节的信号通路将有助于开发治疗牙齿疾病和紊乱的新治疗方法。
