Osteoclast-development patterns and their alterations across Ankylosing Spondylitis(AS)conditions are mysterious,making AS treatment difficult.Our study aims to clarify osteoclast-precursor(OCP)development patterns fr...Osteoclast-development patterns and their alterations across Ankylosing Spondylitis(AS)conditions are mysterious,making AS treatment difficult.Our study aims to clarify osteoclast-precursor(OCP)development patterns from monocytes and their variations under AS conditions.We performed single-cell transcriptomics in peripheral blood mononuclear cells(PBMCs)from healthy donors and AS patients in the early,aggravated and remission stages.After monocytic reclustering,OCP-development patterns and the alterations upon AS onset and different outcomes were revealed based on single-cell trajectory.The trajectories revealed two monocyte states with strong OCP features,and AS pathogenesis was characterized by their reduction.Ribosome synthesis was considered the essential function for the development towards OCP-featured states,and this function and its representative molecule,RPS17,showed a decreasing trend with AS onset and outcomes.Histology assessment showed that RPS17underexpression participated in AS inflammatory osteogenesis and ankylosing destruction.Conditional knockout of RPS17ameliorated ovariectomy-induced bone loss and enhanced osteoclastogenesis,and RPS17 overexpression improved the phenotype of AS-like mice.Importantly,local injection of RPS17-overexpressed monocytic OCPs markedly ameliorated the joint alterations of AS-like mice without promoting bone loss;this was associated with enhanced osteoclastogenesis adjacent to the articular surface and T-cell-suppressive property in monocytic OCPs.Overall,the evolution of monocytes towards OCP-lineage fate mainly depends on ribosome synthesis,and OCP-development disorder participates in AS lesions due to a reduction in RPS17-dependent ribosome synthesis.Notably,RPS17-overexpressed monocytic OCPs have translational potential in preventing and treating AS peripheral lesions.展开更多
Colonization and development of the gut microbiome are crucial for the growth and health of calves.In this review,we summarized the colonization,beneficial nutrition,immune function of gut microbiota,function of the g...Colonization and development of the gut microbiome are crucial for the growth and health of calves.In this review,we summarized the colonization,beneficial nutrition,immune function of gut microbiota,function of the gut barrier,and the evolution of core microbiota in the gut of calves of different ages.Homeostasis of gut microbiome is beneficial for nutritional and immune system development of calves.Disruption of the gut microbiome leads to digestive diseases in calves,such as diarrhea and intestinal inflammation.Microbiota already exists in the gut of calf fetuses,and the colonization of microbiota continues to change dynamically under the influence of various factors,which include probiotics,diet,age,and genotype.Colonization depends on the interaction between the gut microbiota and the immune system of calves.The abundance and diversity of these commensal microbiota stabilize and play a critical role in the health of calves.展开更多
基金supported by National Natural Science Foundation of China(82472473,81991510,81991511 and 81820108020)Major Scientific Research Project of Health in Fujian Province(20212D01003)+3 种基金Fujian Province Joint Fund Project for Science and Technology Innovation(2021Y9023,2023Y9601)China Postdoctoral Science Foundation(2022M710702)Fujian Provincial Natural Science Foundation Projects(2023J01177,2023J011209,2023J01172)Fujian Provincial Health Technology Project(2023GGA004)。
文摘Osteoclast-development patterns and their alterations across Ankylosing Spondylitis(AS)conditions are mysterious,making AS treatment difficult.Our study aims to clarify osteoclast-precursor(OCP)development patterns from monocytes and their variations under AS conditions.We performed single-cell transcriptomics in peripheral blood mononuclear cells(PBMCs)from healthy donors and AS patients in the early,aggravated and remission stages.After monocytic reclustering,OCP-development patterns and the alterations upon AS onset and different outcomes were revealed based on single-cell trajectory.The trajectories revealed two monocyte states with strong OCP features,and AS pathogenesis was characterized by their reduction.Ribosome synthesis was considered the essential function for the development towards OCP-featured states,and this function and its representative molecule,RPS17,showed a decreasing trend with AS onset and outcomes.Histology assessment showed that RPS17underexpression participated in AS inflammatory osteogenesis and ankylosing destruction.Conditional knockout of RPS17ameliorated ovariectomy-induced bone loss and enhanced osteoclastogenesis,and RPS17 overexpression improved the phenotype of AS-like mice.Importantly,local injection of RPS17-overexpressed monocytic OCPs markedly ameliorated the joint alterations of AS-like mice without promoting bone loss;this was associated with enhanced osteoclastogenesis adjacent to the articular surface and T-cell-suppressive property in monocytic OCPs.Overall,the evolution of monocytes towards OCP-lineage fate mainly depends on ribosome synthesis,and OCP-development disorder participates in AS lesions due to a reduction in RPS17-dependent ribosome synthesis.Notably,RPS17-overexpressed monocytic OCPs have translational potential in preventing and treating AS peripheral lesions.
基金funded by the grants from the National Key R&D Program of China(No.2022YFD1301004)National Natural Science Foundation of China(No.31601962)+1 种基金Fundamental Research Funds for the Central Universities(2662019QD021)Key Laboratory of Molecular Animal Nutrition of Zhejiang University(KLMAN202101 and KLMAN202205)。
文摘Colonization and development of the gut microbiome are crucial for the growth and health of calves.In this review,we summarized the colonization,beneficial nutrition,immune function of gut microbiota,function of the gut barrier,and the evolution of core microbiota in the gut of calves of different ages.Homeostasis of gut microbiome is beneficial for nutritional and immune system development of calves.Disruption of the gut microbiome leads to digestive diseases in calves,such as diarrhea and intestinal inflammation.Microbiota already exists in the gut of calf fetuses,and the colonization of microbiota continues to change dynamically under the influence of various factors,which include probiotics,diet,age,and genotype.Colonization depends on the interaction between the gut microbiota and the immune system of calves.The abundance and diversity of these commensal microbiota stabilize and play a critical role in the health of calves.
