Bone Biomechanical Properties in EP4 Knockout Mice

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.