骨髓间充质干细胞外泌体通过miR-133a/BMP-2轴调控大鼠前交叉韧带重建后腱骨愈合OA
Exosomes Derived from Bone Marrow-Derived Mesenchymal Stem Cells Regulate Tendon Bone Healing Following Anterior Cruciate Ligament Reconstruction in Rats via the miR-133a/BMP-2 Axis
目的:基于 miR-133a/BMP-2 轴,探究骨髓间充质干细胞(BMSCs)外泌体对前交叉韧带重建术后大鼠腱-骨愈合的作用.方法:将 SD 大鼠随机分为对照组、外泌体组、miR-NC 外泌体组、miR-133a inhibitor 外泌体组、miR-133a mimic 外泌体组,每组8 只.通过切断前交叉韧带后进行前交叉韧带重建术来构建前交叉韧带重建大鼠模型.Micro-CT 检测骨隧道骨界面骨体积分数(BV/TV)、骨小梁厚度及骨隧道横截面积,生物力学测试检测各组大鼠的重建后韧带的最大力学载荷,HE 染色检测腱骨界面的病理学改变,番红 O-固绿染色检测腱骨界面组织纤维软骨的形成情况,免疫组织化学染色检测腱骨界面组织中 BMP-2 蛋白的表达及定位.结果:相对于对照组,外泌体组大鼠的大鼠 BV/TV、骨小梁厚度、韧带的最大力学载荷、腱骨界面纤维软骨的形成、BMP-2 增加(P<0.05),骨隧道横截面积、腱骨界面宽度减小(P<0.05);相对于外泌体组,miR-NC 外泌体组的上述病理学指标无显著变化(P>0.05);相对于 miR-NC 外泌体组,miR-133a inhibitor 外泌体组大鼠 BV/TV、骨小梁厚度、韧带的最大力学载荷、腱骨界面纤维软骨的形成、BMP-2 增加(P<0.05),骨隧道横截面积、腱骨界面宽度减小(P<0.05),而 miR-133a mimic 外泌体组大鼠 BV/TV、骨小梁厚度、韧带的最大力学载荷、腱骨界面纤维软骨的形成、BMP-2 减小(P<0.05),骨隧道横截面积、腱骨界面宽度增加(P<0.05).结论:BMSCs 外泌体可以包装和递送 miR-133a 来抑制 BMP-2 的表达,进而抑制前交叉韧带重建大鼠的腱骨愈合过程.
Objective:To investigate the effect of bone marrow mesenchymal stem cells(BMSCs)exo-somes on tendon-bone healing in rats after anterior cruciate ligament reconstruction,based on the miR-133a/BMP-2 axis.Methods:The SD rats were randomly divided into control group,exosome group,miR-NC exo-some group,miR-133a inhibitor exosome group,and miR-133a mimic exosome group,with 8 rats in each group.A rat model of anterior cruciate ligament reconstruction was constructed by performing anterior cruciate ligament reconstruction after the anterior cruciate ligament was severed.Micro-CT was used to detect bone vol-ume fraction(BV/TV),trabecular thickness,and cross-sectional area of the bone tunnel.The biomechanical test was performed to detect the maximum mechanical load of the reconstructed ligament in each group of rats.HE staining was used to detect the pathological changes of the tendon-bone interface.Saffron O-green staining was used to detect the formation of fibrocartilage in tendonosal interface tissues.Immunohistochemical staining was used to detect the expression and localization of BMP-2 protein in tendon interfacial tissue.Results:Com-pared with the control group,the BV/TV,trabecular bone thickness,maximum mechanical load of ligaments,formation of tendonosio-bone interface fibrocartilage,and BMP-2 increased in the exosomes group(P<0.05),and the cross-sectional area of the bone tunnel and the width of the tendon-bone interface decreased(P<0.05).Compared with the exosome group,there was no significant change in the above pathological indices in the miR-NC exosome group(P>0.05).Compared with the miR-NC exosomes group,the BV/TV,trabecu-lar bone thickness,maximum mechanical load of ligaments,formation of tendonosio-bone interface fibrocarti-lage,and BMP-2 increased in miR-133a inhibitor exosomes group(P<0.05),and the cross-sectional area of the bone tunnel and the width of the tendon-bone interface decreased(P<0.05);whereas the BV/TV,tra-becular bone thickness,maximum mechanical load of ligaments,formation of tendonosio-bone interface fibro-cartilage,and BMP-2 decreased in miR-133a mimic exosomes group(P<0.05),and the cross-sectional area of the bone tunnel and the width of the tendon-bone interface increased(P<0.05).Conclusion:Exosomes derived from BMSCs can encapsulate and deliver miR-133a to inhibit BMP-2 expression,thereby suppressing the patellar healing process in rats undergoing anterior cruciate ligament reconstruction.
李海清;尹帅;刘媛媛;张昕悦;李永犇;张海峰;宋效雷
河北省沧州中西医结合医院,河北 沧州 061001河北省沧州中西医结合医院,河北 沧州 061001沧州医学高等专科学校,河北 沧州 061001沧州医学高等专科学校,河北 沧州 061001河北省沧州中西医结合医院,河北 沧州 061001沧州医学高等专科学校,河北 沧州 061001河北省沧州中西医结合医院,河北 沧州 061001
骨髓间充质干细胞外泌体前交叉韧带重建腱骨愈合miR-133aBMP-2
Bone marrow mesenchymal stem cellsExosomesAnterior cruciate ligament recon-structionTendon bone healingmiR-133aBMP-2
《河北医学》 2026 (4)
579-585,7
河北省医学科学研究课题计划资助,(编号:20220038)
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