Efficacy and mechanism of whole body vibration therapy in treatment of steroid-induced osteonecrosis of the femoral head:a osteogenesis-angiogenesis theory-based experimental study
Objective:To observe the outcomes of whole body vibration therapy(WBVT)in treatment of steroid-induced osteonecrosis of the femoral head(SONFH),and to explore its underlying mechanism.Methods:Fifty Sprague-Dawley(SD)rats were randomized into blank group,model group,WBVT group,Yoda1 group,WBVT combined Grammostola spatulata mechanotoxin 4(GsMTx4)group.The rats in mod-el group,WBVT group,Yoda1 group,WBVT combined GsMTx4 group were intervened by lipopolysaccharide and methylprednisolone sodium succinate for inducing SONFH.After successful modeling,the rats in WBVT group,Yoda1 group and WBVT combined GsMTx4 group were further intervened with WBVT,Yoda1(a Piezo1 agonist),as well as WBVT and GsMTx4(a Piezo1 inhibitor),respectively.After the end of intervention,the histopathological changes of the femur head were observed and the percentage of empty lacunae in femur head were calcu-lated;meanwhile,the bone microstructure of the femur head was observed and analyzed;furthermore,the protein expression levels of Piezo1,bone morphogenetic protein 2(BMP2),Runt-related transcription factor 2(Runx2),hypoxia-inducible factor-1α(HIF-1α),vascular endo-thelial growth factoi(VEGF),and cluster of differentiation 31(CD31)/endomucin(EMCN)in femur head were detected.Results:①The re-sults of observation on histopathological changes in femur head tissues of rats.In rats from blank group,the dense and well-arranged trabecu-lae were found within the femur heads;compared with that of blank group,the sparse,small,discontinuous and disordered arranged trabecu-lae were presented within the femur heads in rats of model group;compared with that of model group,the trabeculae increased and relatively neatly arranged within the femur heads in rats of WBVT group and Yoda1 group;whereas,compared with that of WBVT group,the trabecu-lae disorderedly arranged within the femur heads in rats of WBVT combined GsMTx4 group.Besides,the percentage of empty lacunae in fe-mur head was higher in model group,WBVT group,Yoda1 group,WBVT combined GsMTx4 group compared to blank group(P=0.000,P=0.000,P=0.000,P=0.000),and was higher in model group compared to WBVT group and Yoda1 group(P=0.000,P=0.000),and was higher in WBVT combined GsMTx4 group compared to WBVT group(P=0.000).②The results of observation on bone microstruc-ture of femur head in rats.The differences were not statistically significant in bone volume fraction(BVF),trabecular thickness(Tb.Th),trabecular number(Tb.N),and trabecular separation(Tb.Sp)of femur head between WBVT group and blank group,as well as between Yo-da1 group and blank group(P=0.213,P=0.081,P=0.384,P=0.471;P=0.435,P=0.131,P=0.104,P=0.126).The BVF and Tb.Th were smaller,the Tb.N was fewer,while,the Tb.Sp was greater in model group and WBVT combined GsMTx4 group compared to blank group(P=0.000,P=0.000,P=0.000;P=0.000,P=0.000,P=0.000;P=0.000,P=0.000).The BVF and Tb.Th were grea-ter,the Tb.N was more,while,the Tb.Sp was smaller in WBVT group and Yoda1 group compared to model group(P=0.000,P=0.002,P=0.000;P=0.000,P=0.007,P=0.014;P=0.000,P=0.000);while,the comparisons between WBVT group and Yoda1 group re-vealed no significant differences(P=0.194,P=0.223,P=0.332,P=0.071).Additionally,the BVF and Tb.Th were smaller,the Tb.N was fewer,while,the Tb.Sp was greater in WBVT combined GsMTx4 group compared to WBVT group(P=0.002,P=0.021,P=0.000,P=0.000).③The results of detection on the protein expression levels of Piezo1,BMP2,Runx2,HIF-1α and VEGF in femur head of rats.The differences were not statistically significant in the protein expression levels of Piezo1,BMP2,Runx2,HIF-1α and VEGF in femur head of rats between WBVT group and Yoda1 group(P=0.061,P=0.122,P=0.773,P=0.814,P=0.991;P=0.112,P=0.071,P=0.955,P=0.749,P=0.915);while,the protein expression levels of Piezo1,BMP2,Runx2,HIF-1α and VEGF in femur head of rats were lower in model group and WBVT combined GsMTx4 group compared to blank group(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000;P=0.000,P=0.000,P=0.000,P=0.000,P=0.000).The protein expression levels of Piezo1,BMP2,Runx2,HIF-1 α and VEGF in femur head of rats were higher in WBVT group and Yoda1 group compared to model group(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000;P=0.000,P=0.000,P=0.000,P=0.000,P=0.000),while,the comparison between WBVT group and Yoda1 group revealed no significant differences(P=0.962,P=0.179,P=0.214,P=0.990,P=0.975).Additionally,the protein expression levels of Piezo1,BMP2,Runx2,HIF-1 α and VEGF in femur head of rats were lower in WBVT combined GsMTx4 group compared to WBVT group(P=0.000,P=0.000,P=0.000,P=0.000,P=0.000).④The results of detection on the protein expression level of CD31/EMCN in femur head of rats.The protein expression level of CD31/EMCN in femur head of rats was lower in model group and WBVT combined GsMTx4 group compared to blank group(P=0.000,P=0.000),while,the comparisons between WBVT group and blank group,as well as between Yoda1 group and blank group revealed no significant differences(P=0.412,P=0.991).The protein expression level of CD31/EMCN in femur head of rats was higher in WBVT group and Yoda1 group compared to model group(P=0.000,P=0.000),while,was lower in WBVT combined GsMTx4 group compared to WBVT group(P=0.000).Conclusion:WBVT can promote the repair of necrotic tis-sues in femur head.It may work by affecting the HIF-1 α/VEGF axis through up-regulating the expression of Piezo1 protein,thereby promo-ting the formation of type H blood vessels in femur head and improving the blood supply to the femur head.
femur head necrosisglucocorticoidswhole body vibration therapyosteogenesisangiogenesistype H blood vesselsPiezol protein
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