Regulation of human mesenchymal stem cell differentiation by TREM-2

Hum Immunol. 2016 Jun;77(6):476-82. doi: 10.1016/j.humimm.2015.06.005. Epub 2015 Jun 12.

Abstract

Activation of the triggering receptor expressed on myeloid cells 2 (TREM-2) regulates myeloid cell function in vitro. However, the failure to detect TREM-2 protein expression in vivo has hampered studies on immunological and other physiological TREM-2 functions. This study demonstrates that TREM-2 is expressed by human mesenchymal stem cells (h-MSCs) and responds to the toll-like receptor (TLR) ligand lipopolysaccharide (LPS). Knockdown of TREM-2 in h-MSCs using a small interfering RNA (siRNA) reduced the expression levels of TLR2, TLR4, and TLR6, inhibited osteogenic, chondrogenic, and adipogenic differentiation under specific induction conditions, and enhanced LPS-evoked inflammatory cytokine production. Thus, activation of TREM-2 may restrain h-MSC immune activation and promote differentiation for tissue repair.

Keywords: Human mesenchymal stem cells (h-MSCs); TREM-2 (triggering receptor expressed on myeloid cells 2); Toll-like receptors (TLRs).

MeSH terms

  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Cytokines / metabolism
  • Gene Expression Regulation / genetics
  • Humans
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / immunology
  • Membrane Glycoproteins / metabolism*
  • Mesenchymal Stem Cells / physiology*
  • Osteogenesis / genetics
  • RNA, Small Interfering / genetics
  • Receptors, Immunologic / metabolism*
  • Toll-Like Receptors / metabolism
  • Wound Healing

Substances

  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • RNA, Small Interfering
  • Receptors, Immunologic
  • TREM2 protein, human
  • Toll-Like Receptors