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Table 1 The impact of major E-cigarette vapour constituents on bone cell function

From: The impact of E-cigarette vaping and vapour constituents on bone health

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]

  1. 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