{"title":"Wnt3a诱导的LRP6磷酸化可通过激活mTORC1/β-catenin信号增强成骨细胞分化,从而缓解骨质疏松症。","authors":"","doi":"10.1016/j.abb.2024.110169","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Osteoporosis (OP) is a common cause of morbidity and mortality in older individuals. The importance of Wnt3a in osteogenic activity and bone tissue homeostasis is well known. Here, we explored the possible molecular mechanism by which Wnt3a mediates the LRP6/mTORC1/β-catenin axis to regulate osteoblast differentiation in OP.</div></div><div><h3>Methods</h3><div>OP-related key genes were identified through a bioinformatics analysis. A ROS17/2.8 cell differentiation system for rat osteogenic progenitors and a rat model of senile OP were constructed for <em>in vitro</em> and <em>in vivo</em> mechanism verification.</div></div><div><h3>Results</h3><div>Bioinformatics analysis revealed that LRP6 was poorly expressed in OP and may play a key role in the occurrence of OP by affecting osteoblast differentiation. LRP6 knockdown inhibited osteoblast differentiation in an <em>in vitro</em> model. In addition, Wnt3a promoted osteoblast differentiation by inducing LRP6 phosphorylation. Moreover, LRP6 promoted mTORC1 expression, which indirectly promoted β-catenin expression, thus promoting osteoblast differentiation. Finally, an <em>in vivo</em> assay revealed that LRP6 inhibition improved OP.</div></div><div><h3>Conclusion</h3><div>Our study provides evidence that Wnt3a induces phosphorylation of LRP6 to activate the mTORC1/β-catenin axis, thus promoting osteoblast differentiation and ultimately improving OP in aged rats.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Wnt3a-induced LRP6 phosphorylation enhances osteoblast differentiation to alleviate osteoporosis through activation of mTORC1/β-catenin signaling\",\"authors\":\"\",\"doi\":\"10.1016/j.abb.2024.110169\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>Osteoporosis (OP) is a common cause of morbidity and mortality in older individuals. The importance of Wnt3a in osteogenic activity and bone tissue homeostasis is well known. Here, we explored the possible molecular mechanism by which Wnt3a mediates the LRP6/mTORC1/β-catenin axis to regulate osteoblast differentiation in OP.</div></div><div><h3>Methods</h3><div>OP-related key genes were identified through a bioinformatics analysis. A ROS17/2.8 cell differentiation system for rat osteogenic progenitors and a rat model of senile OP were constructed for <em>in vitro</em> and <em>in vivo</em> mechanism verification.</div></div><div><h3>Results</h3><div>Bioinformatics analysis revealed that LRP6 was poorly expressed in OP and may play a key role in the occurrence of OP by affecting osteoblast differentiation. LRP6 knockdown inhibited osteoblast differentiation in an <em>in vitro</em> model. In addition, Wnt3a promoted osteoblast differentiation by inducing LRP6 phosphorylation. Moreover, LRP6 promoted mTORC1 expression, which indirectly promoted β-catenin expression, thus promoting osteoblast differentiation. Finally, an <em>in vivo</em> assay revealed that LRP6 inhibition improved OP.</div></div><div><h3>Conclusion</h3><div>Our study provides evidence that Wnt3a induces phosphorylation of LRP6 to activate the mTORC1/β-catenin axis, thus promoting osteoblast differentiation and ultimately improving OP in aged rats.</div></div>\",\"PeriodicalId\":8174,\"journal\":{\"name\":\"Archives of biochemistry and biophysics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of biochemistry and biophysics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0003986124002911\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of biochemistry and biophysics","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0003986124002911","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Wnt3a-induced LRP6 phosphorylation enhances osteoblast differentiation to alleviate osteoporosis through activation of mTORC1/β-catenin signaling
Objective
Osteoporosis (OP) is a common cause of morbidity and mortality in older individuals. The importance of Wnt3a in osteogenic activity and bone tissue homeostasis is well known. Here, we explored the possible molecular mechanism by which Wnt3a mediates the LRP6/mTORC1/β-catenin axis to regulate osteoblast differentiation in OP.
Methods
OP-related key genes were identified through a bioinformatics analysis. A ROS17/2.8 cell differentiation system for rat osteogenic progenitors and a rat model of senile OP were constructed for in vitro and in vivo mechanism verification.
Results
Bioinformatics analysis revealed that LRP6 was poorly expressed in OP and may play a key role in the occurrence of OP by affecting osteoblast differentiation. LRP6 knockdown inhibited osteoblast differentiation in an in vitro model. In addition, Wnt3a promoted osteoblast differentiation by inducing LRP6 phosphorylation. Moreover, LRP6 promoted mTORC1 expression, which indirectly promoted β-catenin expression, thus promoting osteoblast differentiation. Finally, an in vivo assay revealed that LRP6 inhibition improved OP.
Conclusion
Our study provides evidence that Wnt3a induces phosphorylation of LRP6 to activate the mTORC1/β-catenin axis, thus promoting osteoblast differentiation and ultimately improving OP in aged rats.
期刊介绍:
Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics.
Research Areas Include:
• Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing
• Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions
• Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.