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Tmem100- and Acta2-Lineage Cells Contribute to Implant Osseointegration in a Mouse Model
Authors:Alexander Vesprey  Eun Sung Suh  Didem Göz Aytürk  Xu Yang  Miracle Rogers  Branden Sosa  Yingzhen Niu  Ivo Kalajzic  Lionel B Ivashkiv  Mathias PG Bostrom  Ugur M Ayturk
Affiliation:1. Hospital for Special Surgery, New York, NY, USA

AV and ESS contributed equally to this work.;2. Hospital for Special Surgery, New York, NY, USA;3. Hospital for Special Surgery, New York, NY, USA

Department of Joint Surgery, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, China;4. Department of Genetics and Genome Sciences, University of Connecticut, Farmington, CT, USA;5. Hospital for Special Surgery, New York, NY, USA

Departments of Medicine and Immunology, Weill Cornell Medical College, New York, NY, USA;6. Hospital for Special Surgery, New York, NY, USA

Department of Orthopaedic Surgery, Weill Cornell Medical College, New York, NY, USA

Abstract:Metal implants are commonly used in orthopedic surgery. The mechanical stability and longevity of implants depend on adequate bone deposition along the implant surface. The cellular and molecular mechanisms underlying peri-implant bone formation (ie, osseointegration) are incompletely understood. Herein, our goal was to determine the specific bone marrow stromal cell populations that contribute to bone formation around metal implants. To do this, we utilized a mouse tibial implant model that is clinically representative of human joint replacement procedures. Using a lineage-tracing approach, we found that both Acta2.creERT2 and Tmem100.creERT2 lineage cells are involved in peri-implant bone formation, and Pdgfra- and Ly6a/Sca1-expressing stromal cells (PαS cells) are highly enriched in both lineages. Single-cell RNA-seq analysis indicated that PαS cells are quiescent in uninjured bone tissue; however, they express markers of proliferation and osteogenic differentiation shortly after implantation surgery. Our findings indicate that PαS cells are mobilized to repair bone tissue and participate in implant osseointegration after surgery. Biologic therapies targeting PαS cells might improve osseointegration in patients undergoing orthopedic procedures. © 2021 American Society for Bone and Mineral Research (ASBMR).
Keywords:OSSEOINTEGRATION  BONE MARROW STROMAL CELLS  SINGLE-CELL RNA-SEQ
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