Nicotine modulates bone metabolism-associated gene expression in osteoblast cells

David E. Rothem, Lilah Rothem, Michael Soudry, Aviva Dahan, Rami Eliakim

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

Abstract

Smoking has a broad range of physiological effects, such as being a risk factor in osteoporosis, bone fracture incidence, and increased nonunion rates. Recent studies showed that nicotine has effects at the cellular level in human osteoblast cells. To identify possible mechanisms underlying nicotine-induced changes in osteogenic metabolism, we defined changes in proliferation and osteocalcin, type I collagen, and alkaline phosphatase gene expression after treating human osteosarcoma cells (MG63), with various concentration of nicotine. Nicotine affects cell proliferation in a biphasic manner, including toxic and antiproliferative effects at high levels of nicotine and stimulatory effects at low levels. Moreover, low levels of nicotine upregulated osteocalcin, type I collagen, and alkaline phosphatase gene expression. The increased cell proliferation and gene upregulation induced by nicotine were inhibited by addition of the nicotinic receptor antagonist d-tubocurarine. High nicotine concentrations downregulated the investigated genes. Our results demonstrate, for the first time, that the addition of nicotine concentrations analogous to those acquired by a light to moderate smoker yields increased osteoblast proliferation and bone metabolism, whereas the addition of nicotine concentrations analogous to heavy smokers leads to the opposite effect. The inhibition of these effects by d-tubocurarine suggests that nicotine acts via the nicotinic acetylcholine receptor (nAChR).

Original languageEnglish
Pages (from-to)555-561
Number of pages7
JournalJournal of Bone and Mineral Metabolism
Volume27
Issue number5
DOIs
StatePublished - Sep 2009
Externally publishedYes

Bibliographical note

Funding Information:
This work was partially supported by a Keren Ezvonot Grant from the Ministry of Health (IL) and Rambam Medical Research Foundation Grant #1304.

Keywords

  • Bone metabolism
  • Gene expression
  • Nicotine
  • Osteoblast
  • Proliferation

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