Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus...Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.展开更多
动脉型肺动脉高压(pulmonary arterial hypertension,PAH)是以肺血管病理性重塑和肺动脉压升高为特征的进行性心肺疾病。骨形态发生蛋白受体2(bone morphogenetic protein receptor type 2,BMPR2)信号通路功能异常是驱动PAH发生发展的...动脉型肺动脉高压(pulmonary arterial hypertension,PAH)是以肺血管病理性重塑和肺动脉压升高为特征的进行性心肺疾病。骨形态发生蛋白受体2(bone morphogenetic protein receptor type 2,BMPR2)信号通路功能异常是驱动PAH发生发展的关键分子机制。作为PAH的主要遗传易感因素,约70%的遗传性PAH(heritable PAH,HPAH)和20%的特发性PAH(idiopathic PAH,IPAH)患者携带BMPR2突变。传统观点认为BMPR2通过Smad依赖的经典信号通路调控血管稳态,但近年研究显示其非经典信号通路(如TAK1-MAPK、PI3K-AKT、RhoAROCK等)的异常激活也是驱动PAH进展的关键因素。本文阐述BMPR2非经典信号通路的分子机制及其在PAH中的作用,并介绍靶向这些通路的治疗潜力。展开更多
三阴性乳腺癌(TNBC)是乳腺癌的特殊亚型,具有高度侵袭性且缺乏特异性治疗靶点,整体预后较差。近年来,RNA结合蛋白在肿瘤发生发展中的作用逐渐受到关注。细胞质多聚腺苷酸结合蛋白2(cytoplasmic polyadenylation element binding protein...三阴性乳腺癌(TNBC)是乳腺癌的特殊亚型,具有高度侵袭性且缺乏特异性治疗靶点,整体预后较差。近年来,RNA结合蛋白在肿瘤发生发展中的作用逐渐受到关注。细胞质多聚腺苷酸结合蛋白2(cytoplasmic polyadenylation element binding protein 2,CPEB2)是RNA结合蛋白家族的重要成员,通过介导mRNA翻译调控参与多种细胞活动。CPEB2在TNBC中可能呈低表达状态,其表达变化与肿瘤恶性特征可能具有相关性,然而其精确调控网络仍有待探究。MEK/ERK信号通路在TNBC进展中发挥重要作用,相关研究为探讨CPEB2在TNBC中的潜在分子机制提供了研究背景。本文系统综述了CPEB2在TNBC中的研究进展,以期为未来探索奠定理论基础。展开更多
基金supported by the Natural Science Foundation of Hubei Province of China(Grant No.2023AFB671)the National Natural Science Foundation of China(Grant Nos.82360177 and 82560182)+1 种基金the Key Project of Jiangxi Provincial Natural Science Foundation(Grant No.20224ACB206011)“Xuncheng Talents”Project in Jiujiang City,Jiangxi Province(Grant No.JJXC2023071).
文摘Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.
文摘动脉型肺动脉高压(pulmonary arterial hypertension,PAH)是以肺血管病理性重塑和肺动脉压升高为特征的进行性心肺疾病。骨形态发生蛋白受体2(bone morphogenetic protein receptor type 2,BMPR2)信号通路功能异常是驱动PAH发生发展的关键分子机制。作为PAH的主要遗传易感因素,约70%的遗传性PAH(heritable PAH,HPAH)和20%的特发性PAH(idiopathic PAH,IPAH)患者携带BMPR2突变。传统观点认为BMPR2通过Smad依赖的经典信号通路调控血管稳态,但近年研究显示其非经典信号通路(如TAK1-MAPK、PI3K-AKT、RhoAROCK等)的异常激活也是驱动PAH进展的关键因素。本文阐述BMPR2非经典信号通路的分子机制及其在PAH中的作用,并介绍靶向这些通路的治疗潜力。
文摘三阴性乳腺癌(TNBC)是乳腺癌的特殊亚型,具有高度侵袭性且缺乏特异性治疗靶点,整体预后较差。近年来,RNA结合蛋白在肿瘤发生发展中的作用逐渐受到关注。细胞质多聚腺苷酸结合蛋白2(cytoplasmic polyadenylation element binding protein 2,CPEB2)是RNA结合蛋白家族的重要成员,通过介导mRNA翻译调控参与多种细胞活动。CPEB2在TNBC中可能呈低表达状态,其表达变化与肿瘤恶性特征可能具有相关性,然而其精确调控网络仍有待探究。MEK/ERK信号通路在TNBC进展中发挥重要作用,相关研究为探讨CPEB2在TNBC中的潜在分子机制提供了研究背景。本文系统综述了CPEB2在TNBC中的研究进展,以期为未来探索奠定理论基础。
