Effects of uphill and downhill running exercise on the expression of bone remodeling-related genes in rat peripheral blood mononuclear cells
Objective To explore the relationship between gene expression and bone remodeling in the peripheral blood mononuclear cells(PBMCs)of rats,and identify molecular marker of bone remodel-ing-related in PBMCs that are sensitive to different training modes.Methods Thirty-six 2-month-old Sprague-Dawley(SD)rats were randomly divided into a control group(CON group),an uphill running group(UH group),and a downhill running group(DH group),each of 12.Both the UH group(slope 8°)and the DH group(slope-8°)underwent daily 50-minute platform running at the same speed of 25 m/min,5 times per week,for 12 weeks.Then,their body composition,bone mineral density(BMD),and bone mineral content were measured,and their microstructure of trabecular bone in the distal femur were observed.Moreover,Affymetrix®GeneChip®Rat Genome 230 2.0 Array was employed to detect differential genes expressions in PBMCs,and kobas 3.0 was applied to conduct functional en-richment analysis.Results The body fat percentage of the UH and DH groups was significantly lower than the CON group(P<0.05),while the bone microstructural parameters such as bone volume/total vol-ume(BV/TV)and fractal dimension(FD)of the cancellous bone of the distal femur were significantly higher than the latter group(P<0.05).Moreover,the whole-body muscle,gastrocnemius muscle mass and BMD of the DH group were significantly higher than the CON group(P<0.05),with the increased volume of cancellous bone in the distal femur,and the larger number of bone trabeculae tightly aligned.Meanwhile,the bone trabecular thickness(Tb.Th)increased significantly in the DH group com-pared with the CON group(P<0.05),while the bone surface/volume ratio(BS/BV),trabeculae pattern factor(Tb.Pf)and structure model index(SMI)decreased significantly compared with the latter group(P<0.05).What's more,improved femur morphology and distal BMD(P<0.05)and thickened bone tra-beculae were observed in the DH group,compared with the UH group.A total of 235 differentially ex-pressed genes(DEGs)were detected in PBMCs,of which 71 differed between the DH and UH groups.Moreover,IL-17 was the signaling pathway most significantly enriched,and such DEGs as Cc12,Lcn2,Jun,S100a8 and Mmp9 enriched in the IL-17 signaling pathway,differed between the UH and DH groups and were correlated with the bone quality indexes.Conclusion Platform trainings of dif-ferent slopes have different effects on bone remodeling.Cc12,Lcn2,Jun,S100a8 and Mmp9 genes in PBMCs can be ideal candidates for further study in this field.