Table 1.
The impact of major E-cigarette vapour constituents on bone cell function
| Constituent | Model | Treatment | Proliferation/viability | Gene Expression | ALP Activity | Bone Nodules | Other Cellular Functions | Ref |
|---|---|---|---|---|---|---|---|---|
| Nicotine | Primary human osteoblasts | 3d, 0.01–50 mM |
Up to 0.01 mM increased proliferation, > 1 mM reduced proliferation Reduced proliferation. Cytotoxic at 50 mM |
↑Type I collagen, ostrix, ↓ALP, RUNX2, BSP, osteopontin, osteonectin | – | ↑ with 1 mM | Altered morphology | [24] |
| Primary human osteoblasts | 0.01 μM-10 mM up to 3d | ↑ Proliferation with doses up to 1 μM, ↓ with doses > 0.1 mM | ↑ c-fos with 0.1 μM, 1 h | – | – | – | [25] | |
| Primary human osteoblasts | 0.1 μM, 11 and 21d | Cytotoxic | – | – | – | ↑ H2O2 accumulation, activation of caspase 3 and mitochondrial apoptosis pathways | [26] | |
| Murine cell line (OCCM.30) | – | ↑ PGE2 | ↓ | Time-dependent increase in nitric oxide production | ||||
| Saos-2 cells | 3 mM, up to 14d | – | OPG, PGE2, no change | ↓ | – | – | [27] | |
| MG63 | 0.01 μM- 10 mM 1d- 3d | 0.01–100 μM increased proliferation, 1–10 mM decreased/cytotoxic | Type I Col, ALP, osteocalcin, ↑24 h 0.1 μM-1 mM ↓24 h 1-10 mM, 72 h all dosages | – | – | – | [28] | |
| RAW264.7 cells, Treated with RANKL for 7d | 0.01–1 mM, up to 7d | – | ↑ Carbonic anhydrase, α 7 nAch receptor ↓CatK, MMP-9, and V-ATPase d2 | n/a | n/a | ↓multinuclear osteoclasts with large nuclei | [29] | |
| Flavouring chemicals | MG-63 | Cinnamon flavoured, nicotine-free e-cigarette liquid and condensate, 2d. | ↓ Viability | – | – | – | ↑ in ROS production | [30] |
| U937 and MM6 monocytic cell lines | Diacetyl, cinnamaldehyde, acetoin, maltol, pentanedione, o-vanillin, and coumarin, 0.01–1 mM | ↓ Viability | – | – | – |
↑ IL-8 cytokine secretion ↑ in ROS production |
[31] | |
| Primary human bronchial epithelial (NHBE) cells | Diacetyl or 2,3-pentanedione, for 1d | – | RNA-seq differentially expressed genes: Diacetyl = 163 genes, 2,3-pentanedione = 568 genes | – | – | Disrupting cilia biogenesis | [32] | |
| Carbonyl compounds | Human osteogenic sarcoma cell line (U2OS) | 0.001–4 mM formaldehyde, 1-3d | ↓ Proliferation, viability | – | – | – | – | [33] |
| Human bone marrow stem cells cultured in osteogenic conditions | Acetaldehyde (0.1–0.12 mM) and Acrolein (0.01–0.12 mM) 1-28d | ↓ Proliferation, viability | – | ↓ | ↓ with 0.03 mM acrolein, 0.1 mmol/L acetaldehyde | Altered cell morphology Reduced adherence to titanium surface | [34] | |
| Mouse primary osteoblastic cells/ MC3T3-E1 murine cell line | 0.04% Acetaldehyde, 1-4d | ↓ Proliferation, viability |
↑ PPARγ ↓ RUNX2, osterix |
– | – | Reduced osteoblast differentiation, instead a shift towards adipogenesis | [35] | |
| Rat calvarial osteoblasts, bone marrow stromal cells | 0.002% Acetaldehyde, 1-14d | – | ↓ BMP-2, ALDH2 | ↓ | ↓ | – | [36] |
RUNX2 Runt-related transcription factor 2, BSP Bone sialoprotein, PGE2 Prostaglandin E2, OPG osteoprotegerin, MMP Matrix metalloproteinase, ROS reactive oxygen species, PPAR-γ Peroxisome proliferator-activated receptor gamma, ALDH2 Aldehyde dehydrogenase 2, Saos-2 / MG-63 - human osteoblast-like cell lines derived from patients with osteosarcoma. RAW264.7 a monocyte/macrophage like cell linage, capable of forming multinucleated osteoclast-like cells), ALP Alkaline phosphatase, CatK Cathepsin K