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

J Bone Miner Res. 2021 May;36(5):1000-1011. doi: 10.1002/jbmr.4264. Epub 2021 Feb 26.

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: BONE MARROW STROMAL CELLS; OSSEOINTEGRATION; SINGLE-CELL RNA-SEQ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins
  • Animals
  • Bone and Bones
  • Humans
  • Membrane Proteins
  • Mice
  • Osseointegration*
  • Osteogenesis*
  • Prostheses and Implants
  • Tibia

Substances

  • ACTA2 protein, human
  • Actins
  • Membrane Proteins
  • TMEM100 protein, human
  • Tmem100 protein, mouse