Heterotopic ossification(HO)is a pathological process resulting in aberrant bone formation and often involves synovial lined tissues.During this process,mesenchymal progenitor cells undergo endochondral ossification.N...Heterotopic ossification(HO)is a pathological process resulting in aberrant bone formation and often involves synovial lined tissues.During this process,mesenchymal progenitor cells undergo endochondral ossification.Nonetheless,the specific cell phenotypes and mechanisms driving this process are not well understood,in part due to the high degree of heterogeneity of the progenitor cells involved.Here,using a combination of lineage tracing and single-cell RNA sequencing(sc RNA-seq),we investigated the extent to which synovial/tendon sheath progenitor cells contribute to heterotopic bone formation.For this purpose,Tppp3(tubulin polymerization-promoting protein family member 3)-inducible reporter mice were used in combination with either Scx(Scleraxis)or Pdgfra(platelet derived growth factor receptor alpha)reporter mice.Both tendon injury-and arthroplasty-induced mouse experimental HO models were utilized.Sc RNA-seq of tendon-associated traumatic HO suggested that Tppp3 is an early progenitor cell marker for either tendon or osteochondral cells.Upon HO induction,Tppp3 reporter^(+)cells expanded in number and partially contributed to cartilage and bone formation in either tendon-or joint-associated HO.In double reporter animals,both Pdgfra^(+)Tppp3^(+)and Pdgfra^(+)Tppp3^(-) progenitor cells gave rise to HO-associated cartilage.Finally,analysis of human samples showed a substantial population of TPPP3^(-) expressing cells overlapping with osteogenic markers in areas of heterotopic bone.Overall,these data demonstrate that synovial/tendon sheath progenitor cells undergo aberrant osteochondral differentiation and contribute to HO after trauma.展开更多
The oxidation of oxygen ions and the generation of an anode effect at a low oxygen content of 150 mg/kg were discussed in this paper.Cyclic voltammetry and square-wave voltammetry tests were conducted to explore the a...The oxidation of oxygen ions and the generation of an anode effect at a low oxygen content of 150 mg/kg were discussed in this paper.Cyclic voltammetry and square-wave voltammetry tests were conducted to explore the anodic processes of LiF-NdF_(3)melt after a lengthy period of pre-electrolysis purification at 1000℃(during which the oxygen content reduced from 413 to 150 mg/kg).The oxidation process of oxygen ions was found to have two stages:oxidation product adsorption and CO/CO_(2)gas evolution.The adsorption stage was controlled by diffusion,whereas the gas evolution was controlled by the electrochemical reaction.In comparison with oxygen content of 413 mg/kg,the decrease in the amplitude of the current at low oxygen content of 150 mg/kg was much gentler during the forward scanning process when the anode effect occurred.Fluorine-ion oxidation peaks that occurred at about 4.2 V vs.Li/Li+could be clearly observed in the reverse scanning processes,in which fluorine ions were oxidized and perfluorocarbons were produced,which resulted in an anode effect.展开更多
BACKGROUND: Adult stem cells are surveillance repositories capable of supplying a renewable source of progenitors for tissue repair and regeneration to maintain tissue homeostasis throughout life. Many tissue-residen...BACKGROUND: Adult stem cells are surveillance repositories capable of supplying a renewable source of progenitors for tissue repair and regeneration to maintain tissue homeostasis throughout life. Many tissue-resident stem cells have been identified in situ, which lays the foundation for studying them in their native microenvironment, i.e. the niche. Within the musculoskeletal system, muscle stem cells have been unequivocally identified in the mouse, which have led to considerable advances in understanding their role in muscle homeostasis and regeneration. On the other hand, for bone and tendon progenitor cells, mesenchymal stem cells have been used as the main in vitro cell model as they can differentiate into osteogenic, chondrogenic and tenogenic fates. Despite considerable efforts and employment of modern tools, the in vivo origins of bone and tendon stem cells remain debated. Tendon regeneration via stem cells is understudied and deserves attention as tendon damage is noted for a bleak, time-consuming recovery and the repaired tendon seldom regains the structural integrity and strength of the native, uninjured state. OBJECTIVE: Here we review the past efforts and recent studies toward defining adult tendon stem cells and understanding tendon regeneration instead of tendon development. The focus is on adult tendon resident cells in situ and the uncertainty of their roles in regeneration. METHODS: A systematic literature search using the Pubmed search engine was conducted encompassing the seminal papers in the tendon field. CONCLUSIONS: Investigation of tendon stem cells in situ is in its infancy mainly due to lack of necessary tools and standardized injury model. We propose a concerted effort toward establishing a comprehensive cell atlas of the tendon, making genetic tools and choosing a reliable injury model for coordinated studies among different laboratories. Increasing our basic understanding should aid future therapeutic innovations to shorten and enhance the tendon repair/regeneration process.展开更多
基金funded by the NIH/NIAMS (R01 AR070773,R01 AR068316,R01 DE031028,R21 AR078919)USAMRAA through the Peer Reviewed Medical Research Program (W81XWH-18-1-0121,W81XWH-18-1-0336)+4 种基金the Peer Reviewed Orthopaedic Research Program (W81XWH-20-10795)Broad Agency Announcement (W81XWH-1810613)the American Cancer Society (Research Scholar Grant,RSG-18-027-01-CSM)the Maryland Stem Cell Research Foundationfunded by the NIH (R01 AR079171,R01 AR078324,and R01 AR071379)。
文摘Heterotopic ossification(HO)is a pathological process resulting in aberrant bone formation and often involves synovial lined tissues.During this process,mesenchymal progenitor cells undergo endochondral ossification.Nonetheless,the specific cell phenotypes and mechanisms driving this process are not well understood,in part due to the high degree of heterogeneity of the progenitor cells involved.Here,using a combination of lineage tracing and single-cell RNA sequencing(sc RNA-seq),we investigated the extent to which synovial/tendon sheath progenitor cells contribute to heterotopic bone formation.For this purpose,Tppp3(tubulin polymerization-promoting protein family member 3)-inducible reporter mice were used in combination with either Scx(Scleraxis)or Pdgfra(platelet derived growth factor receptor alpha)reporter mice.Both tendon injury-and arthroplasty-induced mouse experimental HO models were utilized.Sc RNA-seq of tendon-associated traumatic HO suggested that Tppp3 is an early progenitor cell marker for either tendon or osteochondral cells.Upon HO induction,Tppp3 reporter^(+)cells expanded in number and partially contributed to cartilage and bone formation in either tendon-or joint-associated HO.In double reporter animals,both Pdgfra^(+)Tppp3^(+)and Pdgfra^(+)Tppp3^(-) progenitor cells gave rise to HO-associated cartilage.Finally,analysis of human samples showed a substantial population of TPPP3^(-) expressing cells overlapping with osteogenic markers in areas of heterotopic bone.Overall,these data demonstrate that synovial/tendon sheath progenitor cells undergo aberrant osteochondral differentiation and contribute to HO after trauma.
基金the National Natural Science Foundation of China(No.51774145).The“Minjiang Scholar”Program of Department of Education,Fujian Province,China was also acknowledged.
文摘The oxidation of oxygen ions and the generation of an anode effect at a low oxygen content of 150 mg/kg were discussed in this paper.Cyclic voltammetry and square-wave voltammetry tests were conducted to explore the anodic processes of LiF-NdF_(3)melt after a lengthy period of pre-electrolysis purification at 1000℃(during which the oxygen content reduced from 413 to 150 mg/kg).The oxidation process of oxygen ions was found to have two stages:oxidation product adsorption and CO/CO_(2)gas evolution.The adsorption stage was controlled by diffusion,whereas the gas evolution was controlled by the electrochemical reaction.In comparison with oxygen content of 413 mg/kg,the decrease in the amplitude of the current at low oxygen content of 150 mg/kg was much gentler during the forward scanning process when the anode effect occurred.Fluorine-ion oxidation peaks that occurred at about 4.2 V vs.Li/Li+could be clearly observed in the reverse scanning processes,in which fluorine ions were oxidized and perfluorocarbons were produced,which resulted in an anode effect.
文摘BACKGROUND: Adult stem cells are surveillance repositories capable of supplying a renewable source of progenitors for tissue repair and regeneration to maintain tissue homeostasis throughout life. Many tissue-resident stem cells have been identified in situ, which lays the foundation for studying them in their native microenvironment, i.e. the niche. Within the musculoskeletal system, muscle stem cells have been unequivocally identified in the mouse, which have led to considerable advances in understanding their role in muscle homeostasis and regeneration. On the other hand, for bone and tendon progenitor cells, mesenchymal stem cells have been used as the main in vitro cell model as they can differentiate into osteogenic, chondrogenic and tenogenic fates. Despite considerable efforts and employment of modern tools, the in vivo origins of bone and tendon stem cells remain debated. Tendon regeneration via stem cells is understudied and deserves attention as tendon damage is noted for a bleak, time-consuming recovery and the repaired tendon seldom regains the structural integrity and strength of the native, uninjured state. OBJECTIVE: Here we review the past efforts and recent studies toward defining adult tendon stem cells and understanding tendon regeneration instead of tendon development. The focus is on adult tendon resident cells in situ and the uncertainty of their roles in regeneration. METHODS: A systematic literature search using the Pubmed search engine was conducted encompassing the seminal papers in the tendon field. CONCLUSIONS: Investigation of tendon stem cells in situ is in its infancy mainly due to lack of necessary tools and standardized injury model. We propose a concerted effort toward establishing a comprehensive cell atlas of the tendon, making genetic tools and choosing a reliable injury model for coordinated studies among different laboratories. Increasing our basic understanding should aid future therapeutic innovations to shorten and enhance the tendon repair/regeneration process.