Nicotine modulates bone metabolism-associated gene expression in osteoblast cells

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).

Skeletal microstructural abnormalities in postmenopausal women with chronic obstructive pulmonary disease

“…(41,42) Nicotine, a major ingredient in tobacco, has been reported to induce both stimulation and inhibition of proliferation and differentiation of osteoblasts. (43) Rothern and colleagues (44) demonstrated in a cultured human osteoblast-like cell line that nicotine, in low concentrations, increases cell proliferation and expression of genes that mediate bone formation. High concentrations of nicotine were shown to suppress osteoblast activity.…”

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

“…However, a less clear image emerges from other studies, indicating no positive reduction in OA associated with smoking (Wilder et al, 2003). Because it was shown that nicotine exerts both positive and negative modulatory effects as a function of its concentration (Rothem et al, 2009), differences in conclusions from the various studies might depend upon the amount of circulating nicotine in the patient's blood.…”

A review of lifestyle, smoking and other modifiable risk factors for osteoporotic fractures

“…Low levels of nicotine upregulate osteocalcin, type I collagen and alkaline phosphatase gene expression. 22 In human osteoblasts, nicotine induces an increase in tumor necrosis factor-a secretion leading to reduced bone formation by osteoblasts and increased osteoclastic resorption. tumor necrosis factor-a has particularly potent effect on osteoclastogenesis, as it not only promotes RANKL production but synergizes with RANKL to amplify osteoclastogenesis.…”