Nicotine modulates bone metabolism-associated gene expression in osteoblast cells.
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).
Department of Orthopaedic Surgery A, Rambam Health Care Campus, Haifa, 31096, Israel. d_rothem@rambam.health.gov.il
David E
DE
Rothem
Lilah
L
Rothem
Michael
M
Soudry
Aviva
A
Dahan
Rami
R
Eliakim
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008954:Models, Biological; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014403:Tubocurarine / Q000494:pharmacology
D024042:Collagen Type I; D018733:Nicotinic Antagonists; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D015675:Osteocalcin; D009538:Nicotine; D000469:Alkaline Phosphatase; D014403:Tubocurarine