Fig 1.
Schematic of the theoretical model of IVD homeostasis.
(A) Metabolism of nutrients increases metabolites levels and reduces pH in the disc. (B) IGF-1 up-regulates cell proliferation and biosynthesis of ECM components. (C) Nicotine down-regulates cell proliferation and ECM biosynthesis (D) Tobacco smoking reduces solute supply to IVD causing reduction in cell density and ECM biosynthesis.
Fig 2.
The IVD is confined between two vertebral bodies, and due to axial symmetry, only the right upper quadrant of IVD is modeled. The computational domain comprehends 3 regions: NP (gray), AF (purple), and CEP (light blue). Along the lateral surface of the AF and at the CEP, the disc is in contact with the vascular network providing solutes (i.e., nutrients, growth factor, binding proteins and nicotine). Sketch dimensions are ho = 5.5 mm, h1 = 0.6 mm, ro = 15.5 mm, r1 = 4.3 mm, and r2 = 2.0 mm.
Fig 3.
Nicotine-mediated down-regulation of cell anabolism and proliferation is dose-dependent (based on in vitro data [20]).
(A) Nicotine-mediated reduction of cell proliferative rate. (B) Nicotine-mediated reduction of GAG production rate.
Table 1.
Boundary conditions of the IVD used in the finite element analyses.
Fig 4.
Nicotine distribution in the IVD.
Data obtained assuming the boundary concentration of nicotine varying from 100nM to 300nM [46]: (A) nicotine boundary concentration of 100nM. (B) nicotine boundary concentration of 300nM.
Fig 5.
Effect of nicotine-mediated down-regulation of cell proliferation and GAG biosynthesis on IVD homeostasis.
(A) Change in cell density in IVD regions. (B) Changes in GAG levels in IVD regions. Data are normalized with respect to the ‘non-smoking’ scenario. Data in blue are obtained assuming a nicotine boundary concentration of 100 nM, those in red assuming a nicotine boundary concentration of 300 nM.
Fig 6.
Effect of reduction of solute supply to IVD due to tobacco smoking on disc homeostasis.
(A) Change in cell density in IVD regions. (B) Change in GAG levels in IVD regions. Data are normalized with respect to the ‘non-smoking’ scenario. Data in blue refer to ‘light smoking’ scenario, those in red to ‘heavy smoking’ scenario.
Fig 7.
Effect of tobacco smoking on disc homeostasis.
(A) Change in glucose concentration in IVD regions. (B) Change in oxygen concentration in IVD regions. (C) Change in cell density in IVD regions. (D) Change in GAG levels in IVD regions. Data are normalized with respect to the ‘non-smoking’ scenario. Data in blue refer to ‘light smoking’ scenario, those in red to ‘heavy smoking’ scenario.
Fig 8.
IVD homeostasis partially recovers at 1 year after quitting smoking.
(A) Change in cell density. (B) Change in GAG concentration. Data are normalized with respect to the ‘non-smoking’ scenario and refer to the CEP (black line), the AF (red line), and the NP (green line). Dotted lines refer to ‘light smoking’ scenario, solid lines (red) to ‘heavy smoking’ scenario.
Fig 9.
Cell density distribution in IVD changes after quitting smoking.
(A) light smoker. (B) heavy smoker. (C) light smoker at 1 year after quitting smoking. (D) heavy smoker at 1 year after quitting smoking. Data are normalized with respect to the ‘non-smoking’ scenario.
Fig 10.
Injection of cells in the innermost NP improves disc homeostasis.
(A) Change of cell density in NP. (B) Change of GAG concentration in NP. Data are normalized with respect to the ‘non-smoking’ scenario. Data in blue refer to ‘light smoking’ scenario, those in red to ‘heavy smoking’ scenario. For all the data reported, cell injection was performed one year after smoke cessation.