Nagatomo Kanako J, Tompkins Kevin A, Fong Hanson, Zhang Hai, Foster Brian L, Chu Emily Y, Murakami Ayu, Stadmeyer Lisa, Canalis Ernesto, Somerman Martha J
Department of Periodontics, School of Dentistry, [corrected] University of Washington, Seattle, Washington, USA.
Connect Tissue Res. 2008;49(6):391-400. doi: 10.1080/03008200802325060.
Bone morphogenetic proteins (BMPs) and BMP antagonists play a crucial role in the regulation of tooth development. One of the BMP extracellular antagonists, gremlin, is a highly conserved 20.7-kDa glycoprotein. Previously, researchers reported that transgenic mice overexpressing gremlin under the control of the osteocalcin promoter (gremlin OE) exhibit a skeletal phenotype and tooth fragility. To further define the tooth phenotype, teeth and surrounding supporting tissues, obtained from gremlin OE at ages of 4 weeks, 2 months, and 4 months, were examined. The histological results demonstrate that gremlin OE exhibit an enlarged pulp chamber with ectopic calcification and thinner dentin and enamel compared with wild-type control. In vitro studies using murine pulp cells revealed that gremlin inhibited BMP-4 mediated induction of Dspp. These data provide evidence that balanced interactions between BMP agonists/antagonists are required for proper development of teeth and surrounding tissues. It is clear that these interactions require further investigation to better define the mechanisms controlling tooth root formation (pulp, dentin, cementum, and surrounding tissue) to provide the information needed to successfully regenerate these tissues.
骨形态发生蛋白（BMPs）和BMP拮抗剂在牙齿发育的调控中起着关键作用。BMP细胞外拮抗剂之一，gremlin，是一种高度保守的20.7 kDa糖蛋白。此前，研究人员报道，在骨钙素启动子控制下过表达gremlin的转基因小鼠（gremlin OE）表现出骨骼表型和牙齿脆弱性。为了进一步明确牙齿表型，对4周龄、2月龄和4月龄的gremlin OE小鼠的牙齿及周围支持组织进行了检查。组织学结果表明，与野生型对照相比，gremlin OE小鼠的牙髓腔扩大，伴有异位钙化，牙本质和釉质更薄。使用小鼠牙髓细胞进行的体外研究表明，gremlin抑制BMP-4介导的Dspp诱导。这些数据提供了证据，表明BMP激动剂/拮抗剂之间的平衡相互作用是牙齿及周围组织正常发育所必需的。显然，这些相互作用需要进一步研究，以更好地确定控制牙根形成（牙髓、牙本质、牙骨质和周围组织）的机制，从而提供成功再生这些组织所需的信息。
