Bone Biomechanical Properties in EP4 Knockout Mice

Abstract

Among the four prostaglandin E receptor subtypes, EP(4) 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 EP(4) knockout (KO) transgenic mice to strain-matched wild-type (WT) controls. We examined two groups of adult female mice: WT (n = 12) and EP(4) 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 EP(4) KO and WT mice (P > 0.05, Student's t-test). EP(4) 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 EP(4) KO than that in WT mice (P < 0.1). In addition, EP(4) 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 EP(4) has an important role in determining biomechanical competence in the mouse skeleton. Despite similar bone size, the absence of an EP(4) receptor may have removed a necessary link for bone adaptation pathways, which resulted in relatively weaker bone properties.