Study On Changes Of Bone Metabolisim And Its Mechanisim In Farnesoid X Receptor Knockout(FXR-/-)Mice

Part one Changes in bone mineral density with advancing age in Farnesoid X receptor knockout(FXR-/-) miceObjective:To study the changes of bone mineral density (BMD) in Farnesoid X receptor knockout(FXR-/-) mice.Methods:8-week-old,28-week-old,42-week-old male FXR-/-mice and sex-age-matched wild-type(WT) mice were involved in the study. The BMD of the femur was determined by dual-energy X-ray absorptiometry (DXA).Results:Compared with WT mice,at the age of28weeks,the BMD in FXR-/-mice revealed lower than WT mice and there were no differences in8-weeks-old and42-weeks-old mice.Conclusion:FXR-/-mice displayed an decreased bone mass,which showed that Farnesoid X receptor plays an important role in bone metabolism.Part two The preliminary study on the mechanism of osteoporosis in mice knocked out Farnesoid X receptor(FXR-/-)Subject:To investigate mechanisms of decreaced bone mass in mice knocked out Farnesoid X receptor (FXR-/-).Method:There were28-weeks-old male FXR-/-mice(n=6) and wild-type(WT) mice(n=10) involved in the study. The mice were euthanized, bloods were collected from retro-orbital venous plexus,and the sera were separeted. Automatic biochemical analyzer was used to determine the biological parameter phosphorus(P),calcium(Ca). The concentration of25(OH)D in sera were analyzed using enzyme-linked immunosorbent assay(ELISA). RT-PCR assay was used to determine the expression levels of CYP27A1, CYP2R1, GC and DHCR7genes which were key genes regulating vitamin D metabolism. ELISA assay determined the levels of serum OPQ RANKL which were closely related to bone metabolic processes.Results:Compared with WT mice,the concentration of25(OH)D and calcium(Ca) displayed a significant low level, and the concentration of sera phosphorus(P) showed an apparent high level; RT-PCR analysis revealed regulation of vitamin D metabolism genes CYP27A1, CYP2R1, GC decreased notably and DHCR7increased markedly; The levels of sera OPG in FXR-/-mice decreased and RANKL increased signiccantly.Conclusion:The abnormal expression of regulation of vitamin D metabolism genes (CYP27A1, CYP2R1, GC, DHCR7) inducing vitamin D reducing may be one of the possible reasons for bone loss in FXR-/-mice. The disorder of serum levles of OPG, RANKL may strengthen the effects of osteoclast bone resorption directly or indirectly which may be another mechanism of bone loss in FXR-/-mice.