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
A transmission-reflection-combined new method is presented for measuring elastic velocities of rocks and minerals at elevated temperature and pressure,which resolves the problems of gradients of temperature and pressu...A transmission-reflection-combined new method is presented for measuring elastic velocities of rocks and minerals at elevated temperature and pressure,which resolves the problems of gradients of temperature and pressure existing in original sample assembly with a pyrophyllite cube.At room temperature and pressure up to 3 GPa,single-crystal quartz and eclogite were used to provide samples under test,respectively.The results of this work agree with the previous measurements very well within the error range.By the use of this new technique,more precise and reasonable data of elastic properties of rocks and minerals at elevated temperature and pressure can be achieved.展开更多
The fate of subducted carbonates in the lower mantle and at the core-mantle boundary was modelled via experiments in the MgCO3-Fe^0 system at 70-150 GPa and 800-2600 Kin a laser-heated diamond anvil cell.Using in situ...The fate of subducted carbonates in the lower mantle and at the core-mantle boundary was modelled via experiments in the MgCO3-Fe^0 system at 70-150 GPa and 800-2600 Kin a laser-heated diamond anvil cell.Using in situ synchrotro n X-ray diffraction and ex situ transmission electron microscopy we show that the reduction of Mg-carbonate can be exemplified by:6 MgCO3+19 Fe=8 FeO+10(Mg0.6Fe^0.4)O+Fe7 C3+3 C.The presented results suggest that the interaction of carbonates with Fe^0 or Fe^0-bearing rocks can produce Fe-carbide and diamond,which can accumulate in the D"region,depending on its carbon to Fe ratio.Due to the sluggish kinetics of the transformation,diamond can remain metastable at the core-mantle boundary(CMB)unless it is in a direct contact with Fe-metal.In addition,it can be remobilized by redox melting accompanying the generation of mantle plumes.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Supported by the National Natural Science Foundation of China under Grant Nos.10032040 and 49774235Foundation of the Geodynamics Opening Laboratory of High-Pressure and High-Temperature.
文摘A transmission-reflection-combined new method is presented for measuring elastic velocities of rocks and minerals at elevated temperature and pressure,which resolves the problems of gradients of temperature and pressure existing in original sample assembly with a pyrophyllite cube.At room temperature and pressure up to 3 GPa,single-crystal quartz and eclogite were used to provide samples under test,respectively.The results of this work agree with the previous measurements very well within the error range.By the use of this new technique,more precise and reasonable data of elastic properties of rocks and minerals at elevated temperature and pressure can be achieved.
基金This work was supported in part by grants from National Natural Science Foundation of China(No.30328004,No.30571269)National Institutes of Health(R01 GM66258-01).
基金supported byRussian Science Foundation,project No 17-17-01177.AGsupport of the Deep Carbon Observatory through the Alfred P.Sloan Foundation
文摘The fate of subducted carbonates in the lower mantle and at the core-mantle boundary was modelled via experiments in the MgCO3-Fe^0 system at 70-150 GPa and 800-2600 Kin a laser-heated diamond anvil cell.Using in situ synchrotro n X-ray diffraction and ex situ transmission electron microscopy we show that the reduction of Mg-carbonate can be exemplified by:6 MgCO3+19 Fe=8 FeO+10(Mg0.6Fe^0.4)O+Fe7 C3+3 C.The presented results suggest that the interaction of carbonates with Fe^0 or Fe^0-bearing rocks can produce Fe-carbide and diamond,which can accumulate in the D"region,depending on its carbon to Fe ratio.Due to the sluggish kinetics of the transformation,diamond can remain metastable at the core-mantle boundary(CMB)unless it is in a direct contact with Fe-metal.In addition,it can be remobilized by redox melting accompanying the generation of mantle plumes.