Prostaglandin E2 receptor (EP4) selective agonist (ONO-4819.CD) accelerates bone repair of femoral cortex after drill-hole injury associated with local upregulation of bone turnover in mature rats

Tanaka, Masahiro; Sakai, Akinori; Uchida, Soshi; Tanaka, Shinya; Nagashima, Masato; Katayama, Teruaki; Yamaguchi, Kojiro; Nakamura, Toshio

doi:10.1016/j.bone.2004.01.002

Cited by 104 publications

(70 citation statements)

References 24 publications

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“…Second, the inhibitory effect of PSLs on osteoclastogenesis was significantly reversed by an Ab against TGF-bRII, the receptor for the signaling of response to TGF-b1 (43). The effect of PSLs on osteoclastogenesis was also significantly antagonized by SQ22536, an adenylate cyclase inhibitor, thus suggesting the involvement of EP2 and/or EP4 receptors that are coupled to adenylate cyclase (44). The substantial concentration of TGF-b1, which alone could suppress the osteoclastogenesis in BM and OP cell cultures, was estimated to be 800 pg/ml and 650 pg/ml, respectively, because of the relatively high basal level of TGF-b1 in the culture medium (i.e., 300 pg/ml in BM cells, 150 pg/ml in OP cells).…”

Section: Discussionmentioning

confidence: 96%

Phosphatidylserine-Containing Liposomes Inhibit the Differentiation of Osteoclasts and Trabecular Bone Loss

Mei

Kukita

et al. 2010

The Journal of Immunology

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Liposomes containing phosphatidylserine (PS) are engulfed by phagocytes including macrophages, microglia, and dendritic cells. PS liposomes (PSLs) mimic the effects of apoptotic cells on these phagocytes to induce the secretion of anti-inflammatory molecules and to inhibit the maturation of dendritic cells. However, the effects of PSLs on osteoclasts, which are also differentiated from the common myeloid precursors, remain to be determined. This study investigated the effects of PSLs on the osteoclastogenesis. In the rat bone marrow culture system, osteoclast precursors phagocytosed PSLs to secrete TGF-β1 and PGE2, which in turn inhibited osteoclastogenesis through the downregulation of receptor activator for NF-κB ligand, receptor activator of NF-κB, ICAM-1, and CD44. Consistent with these in vitro observations, i.m. injection of PSLs significantly increased the plasma level of TGF-β1 and PGE2 and decreased the expression of receptor activator for NF-κB ligand, receptor activator of NF-κB, and ICAM-1 in the skeletal tissues of ankle joints of rats with adjuvant arthritis (AA). A quantitative analysis using microcomputed tomography revealed that PSLs as well as TGF-β1 together with PGE2 significantly inhibited AA-induced trabecular bone loss. These observations strongly suggest that PSLs generate TGF-β1 and PGE2 release, leading to inhibit osteoclastogenesis and AA-induced trabecular bone loss. Because PS is a component of the cell membrane, PSLs therefore can be a potentially effective pharmacological intervention against abnormal bone loss, such as osteoporosis without deleterious side effects.

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Section: Discussionmentioning

confidence: 96%

Phosphatidylserine-Containing Liposomes Inhibit the Differentiation of Osteoclasts and Trabecular Bone Loss

Mei

Kukita

et al. 2010

The Journal of Immunology

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“…The PGE2 receptors (EP1, EP2, EP3 and EP4 subtypes) belong to the Gprotein-coupled receptor family. A vast and still inconclusive range of studies, developed in knockout mice or carried out by administration of specific agonists and antagonists, have confirmed the subtypes EP2 (18) and EP4 (19) as important mediators of PGE2 anabolic action in bone. Conversely, there have also been reports that PGE2-induced bone resorption is mediated chiefly by EP4 and partially by EP2 (20).…”

Section: Prostaglandins and Bonementioning

confidence: 99%

Prostaglandins and bone: potential risks and benefits related to the use of nonsteroidal anti-inflammatory drugs in clinical dentistry

et al. 2008

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In the skeleton, prostaglandins, mainly PGE 2 produced by osteoblasts under COX-2 stimulation, play either a stimulatory or an inhibitory role in bone metabolism, depending on the physiological or pathological conditions. The anabolic effect occurs largely in response to mechanical forces and in bone fracture healing, whereas PGE 2 -mediated resorption contributes significantly to bone loss in inflammatory diseases and in response to prolonged immobilization.

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“…Two such studies are particularly interesting. The first study was conducted in 12-week-old rats with drill-hole injury in their femoral diaphyses using ONO-4819 as the test agent [22]. The animals were subcutaneously injected with the compound at 0, 10 or 30 μg/kg twice a day for 0, 5, 7, 14, 21 and 28 days after the defect was created.…”

Section: Ep4 Receptor-selective Agonist and Bone Formation And Healingmentioning

confidence: 99%

Prostaglandin E2 receptors in bone formation

Thompson

Paralkar

2007

International Orthopaedics (SICO

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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.

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Prostaglandin E2 receptor (EP4) selective agonist (ONO-4819.CD) accelerates bone repair of femoral cortex after drill-hole injury associated with local upregulation of bone turnover in mature rats

Cited by 104 publications

References 24 publications

Phosphatidylserine-Containing Liposomes Inhibit the Differentiation of Osteoclasts and Trabecular Bone Loss

Phosphatidylserine-Containing Liposomes Inhibit the Differentiation of Osteoclasts and Trabecular Bone Loss

Prostaglandins and bone: potential risks and benefits related to the use of nonsteroidal anti-inflammatory drugs in clinical dentistry

Prostaglandin E2 receptors in bone formation

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