Neural crest-derived mesenchymal stem cells(MSCs)are known to play an essential function during tooth and skeletal development.PRX1+cells constitute an important MSC subtype that is implicated in osteogenesis.However,...Neural crest-derived mesenchymal stem cells(MSCs)are known to play an essential function during tooth and skeletal development.PRX1+cells constitute an important MSC subtype that is implicated in osteogenesis.However,their potential function in tooth development and regeneration remains elusive.In the present study,we first assessed the cell fate of PRX1+cells during molar development and periodontal ligament(PDL)formation in mice.Furthermore,single-cell RNA sequencing analysis was performed to study the distribution of PRX1+cells in PDL cells.The behavior of PRX1+cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model.Although PRX1+cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars,their distribution in third molars is highly limited.The PDL formation is associated with a high number of PRX1+cells;during transplanted teeth PDL reconstruction,PRX1+cells from the recipient alveolar bone participate in angiogenesis as pericytes.Overall,PRX1+cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.展开更多
The immune microenvironment plays a vital role in bone defect repair.To create an immune microenvironment that promotes osteogenesis,researchers are exploring ways to enhance the differentiation of M2-type macrophages...The immune microenvironment plays a vital role in bone defect repair.To create an immune microenvironment that promotes osteogenesis,researchers are exploring ways to enhance the differentiation of M2-type macrophages.Functional peptides have been discovered to effectively improve this process,but they are limited by low efficiency and rapid degradation in vivo.To overcome these issues,peptide with both M2 regulatory and self-assembly modules was designed as a building block to construct an ultrasound-responsive nanofiber hydrogel.These nanofibers can be released from hydrogel in a time-dependent manner upon ultrasound stimulation,activating mitochondrial glycolytic metabolism and the tricarboxylic acid cycle,inhibiting reactive oxygen species production and enhancing M2 macrophage polarization.The hydrogel exhibits advanced therapeutic potential for bone regeneration by triggering M2 macrophages to secrete BMP-2 and IGF-I,accelerating the differentiation of bone marrow mesenchymal stem cells(BMSCs)into osteoblasts.Thus,modularly designed biomimetic ultrashort peptide nanofiber hydrogels provide a novel strategy to rebuild osteogenic immune microenvironments for bone repair.展开更多
基金supported by grants from the Key Project of Chinese National Programs for Research and Development (2016YFC1102705)Shanghai Municipal Science and Technology Major Project (2017SHZDZX01)+2 种基金National Natural Science Foundation Projects of China (81822012, 82061130222, 81771043)Shanghai Academic Leader of Science and Technology Innovation Action Plan (20XD1424000)Shanghai Experimental Animal Research Project of Science and Technology Innovation Action Plan (201409006400)
文摘Neural crest-derived mesenchymal stem cells(MSCs)are known to play an essential function during tooth and skeletal development.PRX1+cells constitute an important MSC subtype that is implicated in osteogenesis.However,their potential function in tooth development and regeneration remains elusive.In the present study,we first assessed the cell fate of PRX1+cells during molar development and periodontal ligament(PDL)formation in mice.Furthermore,single-cell RNA sequencing analysis was performed to study the distribution of PRX1+cells in PDL cells.The behavior of PRX1+cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model.Although PRX1+cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars,their distribution in third molars is highly limited.The PDL formation is associated with a high number of PRX1+cells;during transplanted teeth PDL reconstruction,PRX1+cells from the recipient alveolar bone participate in angiogenesis as pericytes.Overall,PRX1+cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.
基金financially supported by National Key R&D Program of China(2022YFA1103200)National Natural Science Foundation of China(81822012,82061130222,81771043,22075212,21925505,52222306,22075212)+3 种基金Shanghai Academic Leader of Science and Technology Innovation Action Plan(20XD1424000)Innovation Program of Shanghai Municipal Education Commission(2023ZKZD28)the Shanghai Experimental Animal Research Project of Science and Technology Innovation Action Plan(8191101676,201409006400)Shanghai International Scientific Collaboration Fund(21520710100).
文摘The immune microenvironment plays a vital role in bone defect repair.To create an immune microenvironment that promotes osteogenesis,researchers are exploring ways to enhance the differentiation of M2-type macrophages.Functional peptides have been discovered to effectively improve this process,but they are limited by low efficiency and rapid degradation in vivo.To overcome these issues,peptide with both M2 regulatory and self-assembly modules was designed as a building block to construct an ultrasound-responsive nanofiber hydrogel.These nanofibers can be released from hydrogel in a time-dependent manner upon ultrasound stimulation,activating mitochondrial glycolytic metabolism and the tricarboxylic acid cycle,inhibiting reactive oxygen species production and enhancing M2 macrophage polarization.The hydrogel exhibits advanced therapeutic potential for bone regeneration by triggering M2 macrophages to secrete BMP-2 and IGF-I,accelerating the differentiation of bone marrow mesenchymal stem cells(BMSCs)into osteoblasts.Thus,modularly designed biomimetic ultrashort peptide nanofiber hydrogels provide a novel strategy to rebuild osteogenic immune microenvironments for bone repair.