Abnormal variations in expression of LRP5, β-catenin, OPG, RANKL and LGR4 in postmenopausal osteoporotic fractures

Abstract Background: The various osteogenesis and osteoclastogenesis factors including LRP5, β-catenin, OPG, RANKL and LGR4 have been associated with osteoporotic incidence, and can be regulated via the activation of diverse signaling pathways including Wnt/β-catenin, OPG/RANKL and LGR4/RANKL/RANK. This study aimed to analyze the expressions of the factors associated with these three pathways in postmenopausal osteoporotic fracture (PMOPF). Methods: Patientswith proximal tibial fractures were first divided into control group and PMOPF group. Bone samples were obtained from them during surgery and the expressions of RNAs and proteins derived from the bone tissues were analyzed using RT-qPCR and Western Blot. It was observed that as the time of the collected peripheral serum changed, PMOPF group turned into groups A-F, whereas control group were also converted into groups A0-F0. The expression of the selected serum factors was analyzed using ELISA. We then analyzed significant differences in the expression of the factors between groups A-F and groups A0-F0. LRP5, β-catenin, OPG, and LGR4 were found to be underexpressed in PMOPF group, relative to control group, and they were underexpressed in groups A-F, relative to groups A0-F0 respectively. In contrast, RANKL was overexpressed in PMOPF group, and it was overexpressed in groups A-F, relative to groups A0-F0 respectively. Results:LRP5 was expressed as the lowest level in group B (the third day after racture), whereas β-catenin was expressed as the lowest in group C (the seventh day after racture), on the contrary, RANKL was expressed as the highest level in group C and finally, OPG and LGR4 were expressed as the lowest in group E (the twenty-eighth day after fracture). Conclusions:The Wnt/β-catenin, OPG/RANKL and LGR4/RANKL/RANK signaling pathways have been reported to be closely associated with the fracture development or repair in PMOPF. The factors changed at different time intervals in PMOPF patients, which could be potentially associated with the bone repair process in osteoporotic fractures.