Differential Effects of Nicotine and Smoke Condensate on Bone Cell Metabolic Activity (original) (raw)
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Global spine journal, 2012
Previous studies by our group showed that nicotine delivered via a transdermal nicotine patch significantly enhanced posterior spinal fusion rates in rabbits. Nicotine transdermal patches provide a steady serum level; there may be a dose-dependent effect of nicotine on posterior spinal fusion. In an in vitro cell culture model of rabbit bone marrow-derived osteoblast-like cells, cells were exposed to different concentrations of nicotine (0, 20, 40, 80 ng/mL and 10, 100, 250 μg/mL). Wells were stained with an alkaline phosphatase (ALP) staining kit to determine ALP enzyme activity. Cells were stained with Von Kossa for mineralization. A two-way analysis of variance (ANOVA) using dose and time as variables showed significant differences among groups; post hoc analysis showed that the 100-μg/mL dose of nicotine significantly enhanced ALP activity over controls. A one-way ANOVA using dose as the variable showed that the 100- and 250-μg/mL doses had significantly greater mineralization t...
Nicotine Stimulates Osteoclast Resorption in a Porcine Marrow Cell Model
Journal of Periodontology, 2003
Background: Combustible tobacco use is generally linked with accelerated periodontal bone loss and diminished post-surgical wound healing; however, the pathogenesis of this process at the cellular level remains unclear. Nicotine is known to affect human gingival fibroblast orientation, attachment, and β 1 integrin expression, yet little is known about its effects on osteoclasts, the cells most responsible for bone resorption. The purpose of this study was to determine the effects of physiologically relevant nicotine levels on porcine osteoclast function as measured by resorption of calcium phosphate. Methods: Pure nicotine was diluted in medium to the following concentrations: 0.03 µM, 0.15 µM, 0.30 µM, 0.60 µM, and 1.50 µM. Porcine osteoclasts were seeded onto calcium phosphate multi-test slides and incubated at 37°C with half media changes every 24 hours. Cells received 0, 0.15, 0.30, 0.60, and 1.50 µM nicotine, or 25 nM parathyroid hormone (PTH). Osteoclast resorption was quantified by measuring the resorbed surface area of the calcium phosphate substrate. Results: Osteoclast cultures resorbed bone slices and calcium phosphate substrate. All nicotine concentrations and PTH resulted in statistically significantly greater mean percent resorptions than the control group (P <0.05). However, no statistical difference was found between the various nicotine doses or PTH. The number of osteoclasts increased in a linear relationship to the increasing nicotine concentrations; however, no correlation was found between osteoclast number and the amount of resorption. Conclusions: Nicotine is non-toxic to osteoclasts at the clinically relevant levels tested. Nicotine appears to stimulate osteoclast differentiation and resorption of calcium phosphate, the major component of bone. Nicotine-modulated osteoclast stimulation may, in part, explain the increased rapidity of periodontal bone loss and refractory disease incidence in smokers.
Nicotine induced proliferation and cytokine release in osteoblastic cells
International Journal of Molecular Medicine, 2006
Smoking has deleterious effects on osteoporosis and periodontitis both characterized by bone loss. Smoking also interferes with the protective effect that hormone replacement therapy (HRT) has on bone loss. Our study investigated two mechanisms by which smoking may affect bone metabolism: nicotine-induced proliferation and nicotine-induced cytokine secretion in osteoblasts. Two osteoblastic cell models were used: mouse osteoblasts derived from mouse calvaria and human osteoblasts. Thymidine incorporation and immunoassays were used to evaluate proliferation, interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) secretion. Parametric and nonparametric statistical analyses were used for comparisons. The results showed that nicotine induced stimulation and inhibition of proliferation in both osteoblastic cell models. In human osteoblasts, the proliferative and inhibitory effects were also donor dependent. Il-6 secretion showed different patterns in mouse and human osteoblasts. In mouse osteoblasts, nicotine significantly increased IL-6 secretion and estradiol significantly inhibited the nicotine-induced IL-6 release. In human osteoblasts, cells derived from one subject did not respond to nicotine. However, in the second sample, nicotine increased secretion of Il-6 but estradiol did not oppose this effect. In human osteoblasts, nicotine also induced an increase in the TNF-alpha secretion and estradiol opposed this increase. These results suggest that nicotine affects bone metabolism by modulating proliferation, and Il-6 and TNF-alpha secretion. These studies provide a possible explanation for differences in bone loss among subjects who smoke and offer a possible mechanism for the oppositional effect of smoking on HRT in subjects with bone loss.
Effect of nicotine on bone healing in rats - A histological study
2014
Background & Objectives: Nicotine is the major alkaloid in tobacco products ( Nicotiona tabacum ) and a psychoactive ingredient responsible for the Central Nervous System (CNS) effects and tobacco addiction. It's been reported to have effects directly on the small blood vessels in producing vasoconstriction and increased vascular resistance that exerts on the microvasculature inhibiting the angioblastic response during re- vascularization and limits the recruitment of cytokines, Bone Morphogenic Proteins (BMPs), Transforming Growth Factor - � (TGF - �), Platelet Derived Growth Factor (PDGF) and the basic Fibroblast Growth Factor (FGF). This leads to inhibition of re-epithelialization, osteogenesis and cellular healing. This study intends to demonstrate histologically the effect of nicotine on bone healing and the healing of bone defects incorporated with autogenous bone graft in an animal model. Methods: 60 female Wistar rats were used in the study. Nicotine hemisulfate at a dos...
Tobacco induced diseases, 2024
INTRODUCTION Mesenchymal stromal cells (MSCs) play a crucial role in promoting tissue regeneration and healing, particularly in bone tissue. Both smoking and nicotine use are known to delay and inhibit the healing process in patients. This study aims at delineating these cellular effects by comparing the impact of nicotine alone to cigarette smoke with equivalent nicotine content, and shedding light on potential differences in the healing process. METHODS We examined how cigarette smoke and nicotine affect the migration, proliferation, and osteogenic differentiation of human patient-derived MSCs in vitro, as well as the secretion of cytokines IL-6 and IL-8. We measured nicotine concentration of the cigarette smoke extract (CSE) to clarify the role of the nicotine in the effect of the cigarette smoke. RESULTS MSCs exposed to nicotine-concentration-standardized CSE exhibited impaired wound healing capability, and at high concentrations, increased cell death. At lower concentrations, CSE dose-dependently impaired migration, proliferation, and osteogenic differentiation, and increased IL-8 secretion. Nicotine impaired proliferation and decreased PINP secretion. While there was a trend for elevated IL-6 levels by nicotine in undifferentiated MSCs, these changes were not statistically significant. Exposure of MSCs to equivalent concentrations of nicotine consistently elicited stronger responses by CSE and had a more pronounced effect on all studied parameters. Our results suggest that the direct effect of cigarette smoke on MSCs contributes to impaired MSC function, that adds to the nicotine effects. CONCLUSIONS Cigarette smoke extract reduced the migration, proliferation, and osteogenic differentiation in MSCs in vitro, while nicotine alone reduced proliferation. Cigarette smoke impairs the osteogenic and regenerative ability of MSCs in a direct cytotoxic manner. Cytotoxic effect of nicotine alone impairs regenerative ability of MSCs, but it only partly explains cytotoxic effects of cigarette smoke. Direct effect of cigarette smoke, and partly nicotine, on MSCs could contribute to the smoking-related negative impact on long-term bone health, especially in bone healing.
Effects of nicotine on markers of bone turnover in ovariectomized rats
Pan African Medical Journal
Introduction: osteoporosis is characterized by low bone mass and density, as well as change in microarchitecture of bone tissue leading to decreased bone strength. In vitro research shows nicotine can increase osteoblast activity and proliferation, also suppress osteoclast activity. Therefore we explore nicotine anti-resorptive property by in vivo true experimental and randomized posttest only controlled group research that was conducted in 18-20 weeks old Rattus norvegicus. Methods: twenty-five female rats were divided into five groups, with 5 rats per group. The first group represented normal rats (Sham), while the second to fifth group underwent bilateral ovariectomy. The second group serves as positive control group (ovariectomy-only/OVX). The third to fifth group serve as dose 1 (P1-0.25mg/kg), dose 2 (P2-0.5 mg/kg), and Dose 3 (P3-0.75 mg/kg) treatment group receiving daily per-oral nicotine for 28 days, started 3 weeks post-ovariectomy. After 28 days treatment, the serum was checked. Results: nicotine has dose-dependent manner on serum osteocalcin and serum DPD level. Level of osteocalcin in P2 group was significantly lower (Mann-Whitney, p = 0.008) compared to OVX group (59.4% lower). Level of DPD in all group was not significantly different (ANOVA, p < 0.05) but shows lowest level in P2 group. For serum calcitonin level, there's no significant different between groups. Conclusion: nicotine at right low-dose might be able to inhibit osteoclast activity, thus open a possibility of anti-resorptive property of nicotine.
Effect of Nicotine on RANKL and OPG and Bone Mineral Density
Journal of Investigative Surgery, 2014
Aim: The signaling pathway OPG/RANK/RANKL is a key in maintaining the balance between the activity of osteoblasts and osteoclasts in order to prevent bone loss. In this study, our aim was to assess the effects of longterm nicotine exposure on plasma RANKL and OPG levels, tissue RANKL and OPG immunoreactivities, and bone mineral density (BMD) scores in rats. Materials and Methods: Thirty-six Swiss Albino rats weighing 70 ± 10 g were divided into three groups. While the controls (n = 12) were only given normal drinking water, for lowdose nicotine (LDN) group (n = 12) 0.4 mg/kg/day; for high-dose nicotine (HDN) group (n = 12), 6.0 mg/kg/day nicotine was added to drinking water for a year. At the end of 12th month, BMD scores were measured using an Xray absorptiometry and bone turnover was assessed by measuring plasma RANKL and OPG levels and RANKL and OPG immunoreactivities in tail vertebrae of the rats. Results: There was no statistically significant difference in BMD scores of lumbar spine and femoral regions of the nicotine groups in comparison to controls. Plasma OPG levels were found to be significantly higher in HDN group, in comparison to the controls and LDN groups (p = .001) unlike plasma RANKL levels. Tissue RANKL and OPG immunoreactivities decreased significantly in the LDN and HDN groups (p < .001, p < .01, respectively). Conclusions: The results of this study show that nicotine is not primarily responsible for the decrease in BMD frequently seen in smokers. Measuring plasma RANKL and OPG levels did not reflect tissue immunoreactivities.
Skeletal System Biology and Smoke Damage: From Basic Science to Medical Clinic
International Journal of Molecular Sciences, 2021
Cigarette smoking has a negative impact on the skeletal system, as it reduces bone mass and increases fracture risk through its direct or indirect effects on bone remodeling. Recent evidence demonstrates that smoking causes an imbalance in bone turnover, making bone vulnerable to osteoporosis and fragility fractures. Moreover, cigarette smoking is known to have deleterious effects on fracture healing, as a positive correlation between the daily number of cigarettes smoked and years of exposure has been shown, even though the underlying mechanisms are not fully understood. It is also well known that smoking causes several medical/surgical complications responsible for longer hospital stays and a consequent increase in the consumption of resources. Smoking cessation is, therefore, highly advisable to prevent the onset of bone metabolic disease. However, even with cessation, some of the consequences appear to continue for decades afterwards. Based on this evidence, the aim of our revie...