Different levels of the neuronal nitric oxide synthase isoform modulate the rate of osteoclastic differentiation of TIB-71 and CRL-2278 RAW 264.7 murine cell clones

Vanessa Nicolin, Cristina Ponti, Paola Narducci, Vittorio Grill, Roberta Bortul, Marina Zweyer, Mauro Vaccarezza, Giorgio Zauli

Research output: Contribution to journalArticlepeer-review

Abstract

It has been clearly established that osteoclasts, which play a crucial role in bone resorption, differentiate from hematopoietic cells belonging to the monocyte/ macrophage lineage in the presence of macrophage-colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). We have here investigated the M-CSF- and RANKL-induced osteoclastic differentiation of two distinct clones of the murine monocytic/macrophagic RAW 264.7 cell line, known as TIB-71 and CRL-2278, the latter cell clone being defective for the expression of the inducible nitric oxide synthase isoform in response to interferon-γ or lipopolysaccharide. CRL-2278 cells demonstrated a more rapid osteoclastic differentiation than TIB-71 cells, as documented by morphology, tartrate-resistant acid phosphatase positivity, and bone resorption activity. The enhanced osteoclastic differentiation of CRL-2278 was accompanied by a higher rate of cells in the S/G2-M phases of cell cycle as compared to TIB-71. The analysis of nitric oxide synthase (NOS) isoforms clearly demonstrated that only neuronal NOS was detectable at high levels in CRL-2278 but not in TIB cells under all tested conditions. Moreover, the broad inhibitor of NOS activity L-NAME significantly inhibited osteoclastic differentiation of CRL-2278 cells. Altogether, these results demonstrate that a basal constitutive neuronal NOS activity positively affects the RANKL/M-CSF-related osteoclastic differentiation.

Original languageEnglish
Pages (from-to)945-954
Number of pages10
JournalAnatomical Record - Part A Discoveries in Molecular, Cellular, and Evolutionary Biology
Volume286
Issue number2
DOIs
Publication statusPublished - Oct 2005

Keywords

  • Neuronal nitric oxide synthase
  • Osteoclastogenesis
  • RAW 264.7
  • Tartrate-resistant acid phosphatase

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Anatomy

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