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Bone Biomechanical Properties in EP4 Knockout Mice

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Abstract

Among the four prostaglandin E receptor subtypes, EP4 has been implicated as an important regulator of both bone formation and bone resorption; however, the integrated activities of this receptor on bone biomechanical properties have not been examined previously. This study compared the bone biomechanical properties of EP4 knockout (KO) transgenic mice to strain-matched wild-type (WT) controls. We examined two groups of adult female mice: WT (n = 12) and EP4 KO (n = 12). Femurs were tested in three-point bending and the lumbar-4 (L4) vertebral body by compression. Distal femur and vertebral body trabecular bone architecture were quantified using micro-computed tomography. Biomechanical structural parameters (ultimate/yield load, stiffness) were measured and apparent material parameters (ultimate/yield stress, modulus) calculated. Body weights and bone sizes were not different between EP4 KO and WT mice (P > 0.05, Student’s t-test). EP4 KO mice exhibited reduced structural (ultimate/yield load) and apparent material (ultimate/yield stress) strength in the femoral shaft and vertebral body compared to WT (P < 0.05). Vertebral body stiffness and femoral neck ultimate load (structural strength) were marginally lower in EP4 KO than that in WT mice (P < 0.1). In addition, EP4 KO mice have smaller distal femur and vertebral bone volume to total volume (BV/TV) trabecular thickness than WT mice (P < 0.05). These results suggest that the prostaglandin receptor EP4 has an important role in determining biomechanical competence in the mouse skeleton. Despite similar bone size, the absence of an EP4 receptor may have removed a necessary link for bone adaptation pathways, which resulted in relatively weaker bone properties.

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Acknowledgments

We thank Daniel Wells, Nick Glass, Andy Lund, and Bryan McGuckin for their assistance. We also thank Dominique Brees (Pathology Department, Pfizer Global Research and Development) for histopathological assessment of mice. This study was partially supported by funds from the State of Nebraska (LB595).

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Authors and Affiliations

  1. Osteoporosis Research Center, Creighton University, Omaha, NE, USA

    M. P. Akhter & D. M. Cullen

  2. Pfizer Global Research and Development, Groton, CT, USA

    L. C. Pan

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  1. M. P. Akhter
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Correspondence to M. P. Akhter.

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Akhter, M.P., Cullen, D.M. & Pan, L.C. Bone Biomechanical Properties in EP4 Knockout Mice. Calcif Tissue Int 78, 357–362 (2006). https://doi.org/10.1007/s00223-005-0186-5

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  • DOI: https://doi.org/10.1007/s00223-005-0186-5

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