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冲击波介导MAPK通路对成骨细胞分化及骨代谢的影响

Effects of extra-corporeal shockwave therapy on osteoblast differentiation and bone metabolism via regulating MAPK signaling pathway
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摘要 [目的]研究ESWT介导MAPK信号通路对成骨细胞分化及骨代谢的影响。[方法]建立15只骨质疏松大鼠模型,均分为A、B、C三组,A组大鼠给予ESWT治疗,B组大鼠给予ESWT+P38抑制剂,C组为空白对照组,接受假刺激。ESWT治疗8 w后,检测大鼠BMD,留取实验大鼠血清标本,检测血清VEGF、E2及骨代谢指标(ALP、Ca)。股动脉急性大出血法处死大鼠,截取其胫骨,采用Western Bolt法测定MAPK信号相关蛋白水平(P38-MAPK、PERK1/2及P-JNK1/2磷酸化)。[结果] A组大鼠胫骨(0.19±0.03)、腰椎(0.21±0.04)及全身(0.16±0.03)BMD均显著高于B组[(0.14±0.02)、(0.16±0.03)、(0.11±0.02)]与C组[(0.13±0.03)、(0.15±0.02)、(0.12±0.03)],(P<0.05),血清VEGF(0.19±0.02)ng/mL及E2(60.45±13.52)pg/mL水平均显著高于B组[(0.13±0.02)、(39.51±6.65)]与C组[(0.14±0.03)、(40.15±7.03)](P<0.05),血清ALP(32.15±6.74)ng/L及Ca(5.12±1.15)mmol/L水平均显著高于B组[(20.02±7.41)、(2.46±0.46)]与C组[(19.47±6.63)、(2.62±0.53)](P<0.05),而B组及C组大鼠骨密度、血清VEGF、E2及骨代谢相关指标水平无显著性差异(P>0.05);A组MAPK信号通路相关蛋白P38-MAPK(0.83±0.21)、P-ERK1/2(3.84±0.84)及P-JNK1/2(1.08±0.16)表达水平均显著低于B组[(1.21±0.17)、(5.17±0.89)、(1.36±0.22)]与C组[(1.23±0.21)、(5.14±0.77)、(1.41±0.21)](P<0.05)。[结论] ESWT可有效提高OP大鼠骨密度,改善其骨代谢状况,ESWT可能通过MAKP信号通路促进成骨,纠正骨代谢失衡,改善OP相关症状。 [Objective]To investigate the effects of extra-corporeal shockwave therapy(ESWT)on osteoblast differentiation and bone metabolism through regulating mitogen-activated protein kinase(MAPK)signaling pathway.[Method] Fifteen female rats were made into osteoporosis(OP)models through ovariectomy,and equally divided into three groups.Group A received ESWT,group B received ESWT+P38 inhibitor,and group C received sham stimulation.After 8 weeks of ESWT treatment,bone mineral density(BMD),serum vascular endothelial growth factor(VEGF),estrogen(E2)and bone metabolism indexes[alkaline phosphatase(ALP),calcium(CA)]were detected.Rats were killed by right femoral artery phlebotomization,and their tibias were cut off.The levels of MAPK signal-related proteins were measured by Western Bolt method,including the phosphorylation levels of P38-MAPK,PERK1/2 and P-JNK1/2.[Result]BMD of tibia,lumbar spine and whole body were(0.19±0.03),(0.21±0.04)and(0.16±0.03)in group A,which were higher than(0.14±0.02),(0.16±0.03)and(0.11±0.02)in group B,and(0.13±0.03),(0.15±0.02)and(0.12±0.03)in group C,with statistical difference(all P<0.05).Serum expression levels of VECF and E2 were(0.19±0.02)ng/mL and(60.45±13.52)pg/mL in group A,which were higher than(0.13±0.02)and(39.51±6.65)in group B,and(0.14±0.03)and(40.15±7.03)in group C,with statistical difference(all P<0.05).Serum ALP and Ca levels were(32.15±6.74)ng/L and(5.12±1.15)mmol/L in group A,which were higher than(20.02±7.41)and(2.46±0.46)in group B,and(19.47±6.63)and(2.62±0.53)in group C,with statistical difference(all P<0.05).No statistic difference was found in BMD,serum VECF,E2,and bone metabolism-related index levels between group B and C(all P>0.05).The expression levels of MAPK signaling pathway related proteins P38-MAPK,P-ERK1/2 and P-JNK1/2 were(0.83±0.21),(3.84±0.84)and(1.08±0.16)in group A,which were lower than(1.21±0.17),(5.17±0.89)and(1.36±0.22)in group B,and(1.23±0.21),(5.14±0.77)and(1.41±0.21)in group C,with statistical difference(all P<0.05).[Conclusion]ESWT can effectively increase bone density and improve bone metabolism in OP rats.The mechanism may be related to the promotion of osteogenesis and the balance of bone metabolism through MAKP signaling pathway,thus improving OP-related symptoms.
作者 王琼芬 王姣姣 李钰 任超 WANG Qiong-fen;WANG Jiao-jiao;LI Yu;REN Chao(Department of Rehabilitation Medicine,The First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,China)
出处 《生物技术》 CAS 2023年第3期359-363,共5页 Biotechnology
基金 四川养老与老年健康协同创新中心(YLZBZ2013) 四川省卫生健康科研课题普及项目(19PJ189)。
关键词 体外冲击波 MAPK信号通路 成骨细胞分化 血清VEGF E2 骨代谢 extra-corporeal shockwave therapy MAPK signaling pathway osteoblast differentiation serum VEGF E2 bone metabolism
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