基于ERK/BMP-2/Smad信号通路探讨骨松强骨丸调控骨质疏松症大鼠成骨细胞分化的分子机制OA
Molecular Mechanism of Gusong Qianggu Pill in Regulating Osteoblast Differ-entiation in Osteoporotic Rats Based on ERK/BMP-2/Smad Signaling Pathway
目的 探讨骨松强骨丸(GSQGW)调控大鼠成骨细胞分化及改善骨质疏松症的分子机制.方法 将40只SPF级雌性SD大鼠随机分为Sham组、Model组、GSQGW-L组(5 g/kg)、GSQGW-H组(10 g/kg).检测各组大鼠体质量、腰椎骨密度(BMD)、骨组织Ⅰ型胶原(typeⅠcollagen,COL-1)以及相关因子的mRNA与蛋白表达.结果 干预8周后,Model组大鼠体质量较Sham组显著增加,骨密度显著降低(P<0.05);与Model组相比,GSQGW-L、GSQGW-H组大鼠骨密度显著升高,其中GSQGW-H组大鼠骨密度均高于GSQGW-L组(P<0.05);免疫组化结果显示,Sham组骨组织COL-1阳性表达强,棕黄色染色面积大、染色深;Model组阳性表达显著减弱;GSQGW-L组、GSQGW-H组COL-1阳性表达较Model组增强,且GSQGW-H组阳性IOD值高于GSQGW-L组(P<0.05);与Sham组相比,Model组Runx2、Osterix、ALP、OCN蛋白表达显著降低(P<0.05);与Model组相比,GSQGW-L组和GSQGW-H组Runx2、Osterix、ALP、OCN蛋白表达均显著升高(P<0.05),且GSQGW-H组蛋白表达高于 GSQGW-L组(P<0.05);与 Sham组 相 比,Model组 ERK1/2、BMP-2、Smad1/5 mRNA及蛋白表达均显著降低(P<0.05);与Model组相比,GSQGW-L组和GSQGW-H组ERK1/2、BMP-2、Smad1/5 mRNA及蛋白表达均显著升高(P<0.05),GSQGW-H组升高更明显(P<0.05).结论 骨松强骨丸可通过激活ERK/BMP-2/Smad信号通路,促进成骨细胞分化、抑制破骨细胞活性,从而改善骨质疏松大鼠的骨密度和骨微结构,其疗效呈剂量依赖性.
Objective To investigate the molecular mechanism by which Gusong Qianggu Wan(GSQGW)regulates osteoblast differentia-tion and improves osteoporosis in rats.Methods Forty SPF-grade female Sprague-Dawley(SD)rats were randomly divided into the Sham group,Model group,GSQGW-L group(5 g/kg),and GSQGW-H group(10 g/kg).The body weight,lumbar bone mineral density(BMD),type I collagen(COL-1)in bone tissue,as well as the mRNA and protein expressions of related factors were detected in each-group.Results After 8 weeks of intervention,compared with the Sham group,the Model group showed a significant increase in body weight and a significant decrease in BMD(P<0.05).Compared with the Model group,the BMD of rats in the GSQGW-L and GSQGW-H groups was significantly increased,and the BMD in the GSQGW-H group was higher than that in the GSQGW-L group(P<0.05).Immu-nohistochemical results showed that the Sham group had strong positive expression of COL-1 in bone tissue,with a large area of brown-yellow staining and deep color;the positive expression in the Model group was significantly weakened;the positive expression of COL-1 in the GSQGW-L and GSQGW-H groups was stronger than that in the Model group,and the positive integrated optical density(IOD)value in the GSQGW-H group was higher than that in the GSQGW-L group(P<0.05).Compared with the Sham group,the protein ex-pression levels of Runx2,Osterix,ALP,and OCN in the Model group were significantly decreased(P<0.05);compared with the Model group,the protein expression levels of Runx2,Osterix,ALP,and OCN in the GSQGW-L and GSQGW-H groups were significantly in-creased,and the protein expression in the GSQGW-H group was higher than that in the GSQGW-L group(P<0.05).Compared with the Sham group,the mRNA and protein expression levels of ERK1/2,BMP-2,and Smad1/5 in the Model group were significantly decreased(P<0.05);compared with the Model group,the mRNA and protein expression levels of ERK1/2,BMP-2,and Smad1/5 in the GSQGW-L and GSQGW-H groups were significantly increased,and the increase in the GSQGW-H group was more significant(P<0.05).Conclu-sion Gu Song Qiang Gu Wan can activate the ERK/BMP-2/Smad signaling pathway to promote osteoblast differentiation and inhibit os-teoclast activity,thereby improving BMD and bone microstructure in OP rats,with a dose-dependent therapeutic effect.
王辉;李俊青;吴非燃;朱卉敏
河南省洛阳正骨医院/河南省骨科医院 脊柱微创中心,郑州 450000河南省洛阳正骨医院/河南省骨科医院 脊柱微创中心,郑州 450000河南省洛阳正骨医院/河南省骨科医院 脊柱微创中心,郑州 450000河南省洛阳正骨医院/河南省骨科医院 脊柱微创中心,郑州 450000
医药卫生
骨松强骨丸骨质疏松成骨细胞ERK/BMP-2/Smad骨密度
Gu Song Qiang Gu WanosteoporosisosteoblastERK/BMP-2/Smadbone mineral density
《吉林医药学院学报》 2026 (3)
167-172,177,7
2022年度河南省医学科技攻关联合共建项目(LHGJ20220252)
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