Li M, Thompson D D, Paralkar V M
Pfizer Global Research and Development, Groton Laboratories, Mail Stop 8118W-208, Groton, CT, 06340, USA,
Int Orthop. 2007 Dec;31(6):767-72. doi: 10.1007/s00264-007-0406-x. Epub 2007 Jun 26.
Prostaglandins, PGE(2) in particular, have diverse actions on various organs, including inflammation, bone healing, bone formation, embryo implantation, induction of labour and vasodilatation, among others. However, systemic side effects have limited their clinical utility. The pharmacological activities of PGE(2) are mediated through four G protein-coupled receptor subtypes, EP1-EP4. Recent studies have shown that EP2 and EP4 receptors play important roles in regulating bone formation and resorption. EP2 and EP4 receptor-selective agonists have been shown to stimulate local or systemic bone formation, augment bone mass and accelerate the healing of fractures or bone defects in animal models upon local or systemic administration, thus, potentially offering new therapeutic options for enhancing bone formation and bone repair in humans. This review will focus on the studies related to bone formation and bone healing in the EP receptor knockout (KO) mice and the EP2 or EP4 receptor-selective agonist treated animal models.
前列腺素,尤其是PGE(2),对包括炎症、骨愈合、骨形成、胚胎着床、引产和血管舒张等在内的各种器官具有多种作用。然而,全身副作用限制了它们的临床应用。PGE(2)的药理活性是通过四种G蛋白偶联受体亚型EP1-EP4介导的。最近的研究表明,EP2和EP4受体在调节骨形成和骨吸收中起重要作用。在动物模型中,局部或全身给予EP2和EP4受体选择性激动剂已显示可刺激局部或全身骨形成、增加骨量并加速骨折或骨缺损的愈合,因此,有可能为增强人类骨形成和骨修复提供新的治疗选择。本综述将聚焦于与EP受体基因敲除(KO)小鼠以及经EP2或EP4受体选择性激动剂处理的动物模型中骨形成和骨愈合相关的研究。