Prostaglandin E2 receptors in bone formation

Abstract

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.Résumé Les prostaglandines en particulier la PGE 2 ont des actions relativement diverses sur différents organes, notamment en termes d'inflammation, de réparation osseuse, de régénération osseuse, d'implantation embryonnaire, d'induction du travail et de vasodilatation. Ces études ont montré que les récepteurs EP2 et EP4 avaient donc un rôle important dans la régulation de formation osseuse et dans sa résorption. On a pu démontrer que les récepteurs EP2 et EP4 stimulaient de façon locale ou systémique la formation osseuse, augmentaient la masse osseuse et accéléraient la guérison des fractures ou la réparation des défects osseux chez les animaux. Ceci nous offre un nouveau potentiel thérapeutique concernant l'amélioration de la régénération osseuse et la réparation des lésions osseuses chez l'homme. Cette revue permet de mettre en valeur les études relatives à la formation et à la cicatrisation osseuse avec le récepteur EP chez la souris et les récepteurs ajustés EP2, EP4 chez les animaux modèles.

Osteogenic differentiation is synergistically influenced by osteoinductive treatment and direct cell–cell contact between murine osteoblasts and mesenchymal stem cells

“…They are located on the surface of bone, express multiple hormone receptors and various cell surface molecules, and secrete hormones and enzymes that maintain the balance between bone formation and resorption [11,12]. Moreover, osteoblasts initiate the process of mineralization.…”

P2X7 receptors: role in bone cell formation and function

“…Despite this, there is support for a role of the P2X7R in osteocyte signalling, with evidence of P2X7R protein expression and BzATP-induced pore formation in MLO-Y4 osteocytes provided nearly 10 years ago (Li et al 2005). Furthermore, P2X7R-induced pore formation in MLO-Y4 osteocytes was shown to occur in response to fluid shear stress and led to the activation of downstream signals typically involved in mechanically induced bone formation, in particular the release of PGE 2 , Li et al 2007). However, contradictory evidence suggests that inhibiting P2X7R does not prevent fluid flow-induced release of PGE 2 from MLO-Y4 osteocytes (Cherian et al 2005).…”

Nanogel‐based scaffold delivery of prostaglandin E2 receptor–specific agonist in combination with a low dose of growth factor heals critical‐size bone defects in mice

“…Synthetic agonists specific for EP4 receptor have been developed as chemicals, and systemic administration of EP4 receptor agonist (EP4A) by daily injection for 20 days suppressed bone loss in ovariectomized and immobilized rats (9). In addition, continuous minipump infusion for 6 weeks accelerated fracture healing in animal models (12), and administration of EP4A by subcutaneous injection twice daily for 4 weeks also promoted healing of cortical bone defects produced in femora (13). However, bone formation is a long-term process, requiring weeks, and delivery of EP4A still necessitates multiple daily injections or continuous infusion (14,15).…”