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Targeting of iNOS with antisense DNA plasmid reduces cytokine-induced inhibition of osteoblastic activity

Takahiro Abe1, Hisako Hikiji, Wee Soo Shin

  • 1Department of Oral and Maxillofacial Surgery, University of Tokyo, Tokyo, Japan.

American Journal of Physiology. Endocrinology and Metabolism
|March 27, 2003
PubMed

Insights

Antisense DNA targeting inducible nitric oxide synthase (iNOS) in osteoblasts prevents pro-inflammatory cytokine-induced inhibition of bone cell activity. This approach reduces nitric oxide (NO) and peroxynitrite (ONOO-) production, preserving osteoblastic differentiation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Pro-inflammatory cytokines like TNF-α and IL-1β induce excessive nitric oxide (NO) and peroxynitrite (ONOO-) via inducible nitric oxide synthase (iNOS) in osteoblasts.
  • This excessive production can impair osteoblastic activity and differentiation.

Purpose of the Study:

  • To evaluate the effect of antisense DNA targeting iNOS on osteoblastic activity.
  • To develop transformed cell lines for long-lasting inhibition of iNOS.

Main Methods:

  • Generated transformed murine osteoblast cell lines using antisense plasmid targeting the iNOS gene.
  • Confirmed cell line transformation by detecting antisense transcripts, reduced iNOS protein expression, and decreased NO synthase activity and production.
  • Assayed osteoblastic differentiation markers (mRNA expression of type I collagen, alkaline phosphatase, osteocalcin, and Core binding factor) in the presence of pro-inflammatory cytokines.

Main Results:

  • Transformed cell lines exhibited reduced iNOS expression and activity, leading to decreased NO and ONOO- production.
  • These iNOS-targeted cell lines prevented the inhibition of osteoblastic differentiation markers caused by pro-inflammatory cytokines.
  • Antisense DNA targeting iNOS effectively mitigated cytokine-induced suppression of osteoblastic activity.

Conclusions:

  • Antisense DNA targeting iNOS is a potent strategy to counteract the negative effects of pro-inflammatory cytokines on osteoblastic activity.
  • This approach holds potential for therapeutic interventions aimed at preserving bone health in inflammatory conditions.

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