Tppp3~+synovial/tendon sheath progenitor cells contribute to heterotopic bone after trauma  

作　　者：Ji-Hye Yea Mario Gomez-Salazar Sharon Onggo Zhao Li Neelima Thottappillil Masnsen Cherief Stefano Negri Xin Xing Qizhi Qin Robert Joel Tower Chen-Ming Fan Benjamin Levi Aaron W.James 

机构地区：[1]Department of Pathology,Johns Hopkins University,Baltimore,MD 21205,USA [2]Orthopaedic and Trauma Surgery Unit,Department of Surgery,Dentistry,Paediatrics and Gynaecology of the University of Verona,Verona,Italy [3]Center for Organogenesis and Trauma,Department of Surgery,University of Texas Southwestern,Dallas,TX,USA [4]Carnegie Institution for Science,Baltimore,MD,USA

出　　处：《Bone Research》2023年第3期548-559,共12页骨研究（英文版）

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);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 Foundation;funded by the NIH (R01 AR079171,R01 AR078324,and R01 AR071379)。

摘　　要：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.

关 键 词：PROGENITOR TENDON REPORTER 

分 类 号：R68[医药卫生—骨科学]