4.6 Article

Tmem100- and Acta2-Lineage Cells Contribute to Implant Osseointegration in a Mouse Model

Journal

JOURNAL OF BONE AND MINERAL RESEARCH
Volume 36, Issue 5, Pages 1000-1011

Publisher

WILEY
DOI: 10.1002/jbmr.4264

Keywords

OSSEOINTEGRATION; BONE MARROW STROMAL CELLS; SINGLE‐ CELL RNA‐ SEQ

Funding

  1. Hospital for Special Surgery institutional funds
  2. Tow Foundation

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This study identified specific bone marrow stromal cell populations essential for bone formation around metal implants. P alpha S cells are mobilized after surgery to repair bone tissue and participate in implant osseointegration.
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 (P alpha S cells) are highly enriched in both lineages. Single-cell RNA-seq analysis indicated that P alpha S cells are quiescent in uninjured bone tissue; however, they express markers of proliferation and osteogenic differentiation shortly after implantation surgery. Our findings indicate that P alpha S cells are mobilized to repair bone tissue and participate in implant osseointegration after surgery. Biologic therapies targeting P alpha S cells might improve osseointegration in patients undergoing orthopedic procedures. (c) 2021 American Society for Bone and Mineral Research (ASBMR).

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