Effects of a prostaglandin EP4 agonist, ONO-4819, and risedronate on trabecular microstructure and bone strength in mature ovariectomized rats

Ito, Masako; Nakayama, Keiji; Konaka, Akira; Sakata, Kozue; Maruyama, Takayuki

doi:10.1016/j.bone.2006.02.054

Cited by 34 publications

(23 citation statements)

References 33 publications

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“…Contrary to this discrepancy between studies using genetically modified mice, most studies using pharmacological approaches have suggested that EP4 activation has anabolic effects in bone. EP4 agonists (ONO-4819) delivered via local or systemic administration increased bone mass and strength in intact rats (Ninomiya et al, 2011) and in ovariectomized rats as an osteoporosis model (Yoshida et al, 2002;Ito et al, 2006;Ke et al, 2006). In a different model of osteoporosis induced through immobilization, ONO-4819 also completely blocked bone loss in rats when infused systemically (Yoshida et al, 2002).…”

Section: Other Immune Cellsmentioning

confidence: 99%

“…Recent findings have suggested that the regulation of EP4 signaling could be involved in therapeutic strategies for colon cancer Yang et al, 2006), aortic aneurysm (Cao et al, 2012;Yokoyama et al, 2012), rheumatoid arthritis Okumura et al, 2008;Chen et al, 2010), osteoporosis (Yoshida et al, 2002;Ito et al, 2006;Ke et al, 2006), and autoimmune disease (Yao et al, 2009). Accordingly, the regulation of EP4 signaling has received even greater attention as a potential therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Prostanoid EP4 Receptor and Its Signaling Pathway

Yokoyama

Iwatsubo²,

Umemura³

et al. 2013

Pharmacol Rev

217

257

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Section: Other Immune Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Prostanoid EP4 Receptor and Its Signaling Pathway

Yokoyama

Iwatsubo²,

Umemura³

et al. 2013

Pharmacol Rev

217

257

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“…24 Moreover, mFEA of excised bones is non-destructive allowing for subsequent histological analysis. Although a number of studies involving rodents have used mFEA to determine the effect of drug treatment on bone strength, [25][26][27][28][29][30] there is little evidence in the literature establishing that mFEA can accurately predict the mechanical properties of rodent bone, and especially murine bones. Of the few studies comparing FEA predictions to experimental measurements of strength in rodent tissues, long bones were tested with limited examination of material definitions.…”

Section: Introductionmentioning

confidence: 99%

Predicting mouse vertebra strength with micro-computed tomography-derived finite element analysis

Nyman¹,

Uppuganti²,

Makowski³

et al. 2015

BoneKEy Reports

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As in clinical studies, finite element analysis (FEA) developed from computed tomography (CT) images of bones are useful in pre-clinical rodent studies assessing treatment effects on vertebral body (VB) strength. Since strength predictions from microCT-derived FEAs (mFEA) have not been validated against experimental measurements of mouse VB strength, a parametric analysis exploring material and failure definitions was performed to determine whether elastic mFEAs with linear failure criteria could reasonably assess VB strength in two studies, treatment and genetic, with differences in bone volume fraction between the control and the experimental groups. VBs were scanned with a 12-mm voxel size, and voxels were directly converted to 8-node, hexahedral elements. The coefficient of determination or R 2 between predicted VB strength and experimental VB strength, as determined from compression tests, was 62.3% for the treatment study and 85.3% for the genetic study when using a homogenous tissue modulus (E t ) of 18 GPa for all elements, a failure volume of 2%, and an equivalent failure strain of 0.007. The difference between prediction and measurement (that is, error) increased when lowering the failure volume to 0.1% or increasing it to 4%. Using inhomogeneous tissue density-specific moduli improved the R 2 between predicted and experimental strength when compared with uniform E t ¼ 18 GPa. Also, the optimum failure volume is higher for the inhomogeneous than for the homogeneous material definition. Regardless of model assumptions, mFEA can assess differences in murine VB strength between experimental groups when the expected difference in strength is at least 20%.

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“…PGE 2 stimulates bone formation and bone resorption via the EP4 receptor. EP4 agonist is an effective bone anabolic agent in rats (Hagino et al 2005, Ito et al 2006; however, the efficacy of the anabolic effect in mice is limited (Kato et al 2007). In regards to the bone phenotype in EP4-knockout animals, Figure 5 Adult PGIS K/K mice have increased bone turnover activity.…”

Section: Discussionmentioning

confidence: 99%

Increased bone mass in adult prostacyclin-deficient mice

Nakalekha

Yokoyama

Miura³

et al. 2009

Journal of Endocrinology

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Prostaglandins (PGs) are key regulatory factors that affect bone metabolism. Prostaglandin E 2 (PGE 2 ) regulates bone resorption and bone formation. Prostacyclin (PGI 2 ) is one of the major products derived from arachidonic acid by the action of cyclooxygenase and PGI 2 synthase (PGIS). Unlike PGE 2 , there are few reports about the role of PGI 2 in bone regulation. Therefore, we investigated the potential effect of PGI 2 on bone metabolism. We used PGIS knockout (PGIS K/K ), PGIS heterozygous (PGIS C/K

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Effects of a prostaglandin EP4 agonist, ONO-4819, and risedronate on trabecular microstructure and bone strength in mature ovariectomized rats

Cited by 34 publications

References 33 publications

The Prostanoid EP4 Receptor and Its Signaling Pathway

The Prostanoid EP4 Receptor and Its Signaling Pathway

Predicting mouse vertebra strength with micro-computed tomography-derived finite element analysis

Increased bone mass in adult prostacyclin-deficient mice

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