PLAP-1/asporin, a novel negative regulator of periodontal ligament mineralization
PLAP-1/asporin, a novel negative regulator of periodontal ligament mineralization
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DOI：
10.1074/jbc.m611181200
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发表时间：
2007-08-10
影响因子：
4.8
通讯作者：
Murakami, Shinya
中科院分区：
文献类型：
--
作者：
Yamada, Satoru;Tomoeda, Miki;Murakami, Shinya
牙周膜相关蛋白-1(PLAP-1)/asporin是最近发现的富含亮氨酸的小重复蛋白多糖家族的新成员。PLAP-1/asporin参与软骨形成，并被认为参与了骨关节炎的发病机制。我们报道PLAP-1/asporin也在牙周膜(PDL)中特异和主要地表达，并且它负向调节PDL细胞的矿化。原位杂交分析表明，PLAP-1/asporin不仅在萌出牙的牙周膜中特异表达，而且在牙囊中也有表达，牙囊是牙周膜发育过程中牙周膜的前体组织。PLAP-1/asporin在小鼠PDL来源的克隆细胞中的过表达干扰了自然和骨形态发生蛋白2(BMP-2)诱导的PDL细胞矿化。另一方面，RNA干扰下调PLAP-1/asporin转录水平可增强BMP-2对PDL细胞的诱导分化作用。免疫共沉淀实验显示PLAP1/asporin与BMP-2在体外有直接的相互作用，免疫组织化学染色显示PLAP-1/asporin与BMP-2在细胞水平上存在共定位。这些结果提示，PLAP-1/asporin在牙周膜中作为细胞分化和矿化的负调控因子发挥着特殊的作用(S)，其机制可能是通过调节BMP-2的活性来阻止牙周膜发生非生理性矿化，如强直。
Periodontal ligament-associated protein-1 (PLAP-1)/asporin is a recently identified novel member of the small leucine-rich repeat proteoglycan family. PLAP-1/asporin is involved in chondrogenesis, and its involvement in the pathogenesis of osteoarthritis has been suggested. We report that PLAP-1/asporin is also expressed specifically and predominantly in the periodontal ligament (PDL) and that it negatively regulates the mineralization of PDL cells. In situ hybridization analysis revealed that PLAP-1/asporin was expressed specifically not only in the PDL of an erupted tooth but also in the dental follicle, which is the progenitor tissue of the PDL during tooth development. Overexpression of PLAP-1/asporin in mouse PDL-derived clone cells interfered with both naturally and bone morphogenetic protein 2 (BMP-2)-induced mineralization of the PDL cells. On the other hand, knockdown of PLAP-1/asporin transcript levels by RNA interference enhanced BMP-2-induced differentiation of PDL cells. Furthermore co-immuno-precipitation assays showed a direct interaction between PLAP1/asporin and BMP- 2 in vitro, and immunohistochemistry staining revealed the co-localization of PLAP-1/asporin and BMP- 2 at the cellular level. These results suggest that PLAP-1/asporin plays a specific role(s) in the periodontal ligament as a negative regulator of cytodifferentiation and mineralization probably by regulating BMP- 2 activity to prevent the periodontal ligament from developing non-physiological mineralization such as ankylosis.