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Related Experiment Videos

TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function.

Mary Beth Humphrey1, Michael R Daws, Steve C Spusta

  • 1Department of Medicine, VA Medical Center and University of California, San Francisco, California 94121, USA. nbh@itsa.ucsf.edu

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
|January 19, 2006
PubMed
Summary

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Triggering receptor expressed in myeloid cells-2 (TREM2) regulates osteoclast (OC) function, including multinucleation, migration, and resorption. These findings highlight TREM2

Area of Science:

  • Immunology and Bone Biology
  • Cellular and Molecular Biology

Background:

  • TREM2 (triggering receptor expressed in myeloid cells-2) is a receptor that associates with the signaling adapter DAP12 in osteoclasts (OCs).
  • Genetic mutations in TREM2 or DAP12 are linked to Nasu-Hakola disease, a human disorder affecting the brain and bones.
  • Previous research established the critical role of ITAM signals through DAP12 and FcRgamma in OC development.

Purpose of the Study:

  • To investigate the specific role of TREM2 in mouse osteoclast (OC) development and function.
  • To analyze TREM2's contribution to OC migration and bone resorption in vitro.
  • To elucidate TREM2's regulatory mechanisms in OC differentiation and function, independent of DAP12.

Main Methods:

  • Generation of monoclonal anti-mouse TREM2 antibodies (mAb).

Related Experiment Videos

  • Analysis of TREM2 surface expression on pre-osteoclasts and mature OCs using flow cytometry.
  • Assessment of antibody ligation effects on OC differentiation, resorption, and migration in vitro.
  • Disruption of TREM2 expression using RNA interference (RNAi) in pre-osteoclast cell lines.

    • Main Results:

    • TREM2 expression is upregulated during OC differentiation from bone marrow macrophages (BMMs) and RAW264.7 precursors.
    • Anti-TREM2 mAb treatment enhanced multinucleated OC formation, while blockade of TREM2 decreased OC resorption and migration.
    • TREM2 RNAi led to a loss of OC formation, and TREM2 signaling was independent of DAP12 in certain contexts.

    Conclusions:

    • The TREM2 receptor plays a significant role in regulating osteoclast (OC) multinucleation, resorption, and migration.
    • TREM2-DAP12 signaling pathways are crucial for both OC formation and the functional activities of mature OCs.
    • TREM2 regulates OC function independently of its effects on multinucleated OC differentiation.