Table 3.
Effects of lithium on bone cells in vitro.
| Type of bone cell | Treatment | Findings | References |
|---|---|---|---|
| Murine osteoblast precursor (C3H10T1/2) cells | LiCl (10 mM) | ALP activity: ↑, p-β-catenin: ↓, Runx-2: ↑ | (Arioka et al., 2014) |
| Primary osteoblasts from calvariae of 3-day-old rats | LiCl (10 mM) | p-Akt: ↔, p-GSK3β: ↑, p-β-catenin: ↓, NFATc1: ↓, ALP activity: ↑ | (Bai et al., 2019) |
| LiCl (5 mM) + LY294002 (5 μM) | p-Akt: ↑, p-GSK3β: ↑, p-β-catenin: ↓, NFATc1: ↓, ALP activity: ↑ | ||
| Calvaria cells recovered from Lrp5-knockout mice | LiCl (20 mM) | Percent of apoptotic calvarial osteoblast cells: ↓, cell differentiation into adipocyte lineage: ↓ | (Clement-Lacroix et al., 2005) |
| MSCs derived from Lrp5-knockout mice | ALP activity: ↑, COL1α1: ↑ | ||
| Rat bone marrow MSCs stimulated with titanium particles | LiCl (1 or 5 mM) | ALP: ↑, extracellular matrix mineralization: ↑ | (Yang et al., 2019) |
| Bone marrow MSCs from male Sprague-Dawley rats | Li-SLA coated titanium discs | ALP: ↑, OCN: ↑, COL1: ↑, Runx-2: ↑, BMP-2: ↑, β-catenin: ↑, OPG: ↑, RANKL: ↔ | (Huang et al., 2019) |
| Bone marrow MSCs | Li-nHA | ALP-positive cells: ↑, calcium nodule: ↑, COL1: ↑, formation of lipid: ↓, p-GSK3β: ↑, β-catenin: ↑, Runx-2: ↑, Akt: ↑, PPAR-γ: ↓ | (Li et al., 2018) |
| Murine pluripotent mesenchymal (C2C12) cells | Li-SLA coated titanium discs (1 mM) | ALP: ↑, OPG: ↑ | (Galli et al., 2013) |
| Murine calvaria MC3T3 cells | OPG: ↑, OCN: ↑ | ||
| Primary murine bone marrow cells | ALP: ↑, CTGF: ↑, Wisp2: ↑, Cox-2: ↑, OPG: ↔, Runx-2: ↔, COL1α1: ↔, OCN: ↑, ALP activity: ↑ | ||
| Rat bone marrow MSCs | Lithium-doped mesoporous silica nanospheres (0.3–0.5 mg/mL) | Cell proliferation: ↑, ALP activity: ↑, Runx-2: ↑, ALP: ↑, OCN: ↑, OPN: ↑ | (Zhang et al., 2018a) |
| Bone marrow stromal cells from adult Sprague-Dawley rats | LPPK | Cell proliferation: ↑, ALP activity: ↑ | (Zhang et al., 2018b) |
| MC3T3-E1 cells | LiCl (50 or 100 mM)/CPC extract | Cell proliferation: ↑, ALP activity: ↑, osteogenic mineralization: ↑, spreading & extension of filopodia: ↑, COL1α1: ↑, OCN: ↑, OPG: ↑, Runx-2: ↑, p-GSK3β: ↑, p-β-catenin: ↓ | (Li et al., 2017a) |
| Human osteosarcoma (MG63) cells | LiCl (50 or 100 mM)/CPC extract | Cell attachment and growth were supported, cell proliferation: ↑, ALP activity: ↑ | (Li et al., 2017b) |
| Human osteosarcoma (MG63) cells | Li-DBB scaffold | Cell proliferation activities: ↑, calcium deposition: ↑ | (Guo et al., 2018) |
| Human osteosarcoma (MG63) cells | Li-MAO-ETP scaffold | Cell viability: ↑, ALP activity: ↑, OPN: ↑, OCN: ↑, COL1α1: ↑, Runx-2: ↑, LRP5: ↑, LRP6: ↑, Axin2: ↑, β-catenin: ↑, p-β-catenin: ↓, p-GSK3β: ↑ | (Liu et al., 2018) |
| Human osteosarcoma (MG63) cells | Li-CPP scaffold (2%) | Cell viability: ↑, GSK3β: ↓, β-catenin: ↑, Runx-2: ↑, ALP: ↑, mineralized nodule: ↑, calcium deposition: ↑ | (Ma et al., 2019) |
| Murine pre-osteoblastic (MC3T3-E1) cells | LiCl (10 mM) | Mineral deposition: ↓, cell proliferation: ↑, ALPL activity: ↓, Runx-2: ↓, OSX: ↓, Alpl: ↓, OCN: ↓, p-SMAD1/5/8: ↓, p-p38: ↔, p-ERK1/2: ↔ | (Li et al., 2011) |
| Mouse primary osteoblasts | Expression of Runx-2, OSX, Atf4, Dlx5, Alpl, COL1α1, Ibsp, Spp1 and OCN at day 3: ↓, the inhibited osteoblast differentiation was diminished at day 6 and completely abolished at day 9. | ||
| Murine pluripotent mesenchymal (C2C12) cells | Runx-2: ↓, OSX: ↓, Alpl: ↓, OCN: ↓, p-SMAD1/5/8: ↓, p-p38: ↔, p-ERK1/2: ↔, SMAD6: ↓, SMAD7: ↓ | ||
| Murine osteoclast precursor (RAW-D) cells treated with RANKL | LiCl (10 mM) | TRAP activity: ↓, TRAP-positive multinucleated cells: ↓, NFATc1: ↓ | (Arioka et al., 2014) |
| Bone marrow macrophages treated with M-CSF and RANKL | LiCl (10 mM) | p-Akt: ↔, p-GSK3β: ↑, p-β-catenin: ↓, NFATc1: ↓, pit area: ↓, TRAP: ↓ | (Bai et al., 2019) |
| LiCl (5 mM) + LY294002 (5 μM) | p-Akt: ↑, p-GSK3β: ↑, p-β-catenin: ↓, NFATc1: ↓, pit area: ↓, TRAP: ↓ | ||
| RAW264.7 macrophages stimulated with titanium particles | LiCl (1 or 5 mM) | TNF-α: ↓, IL-6: ↓, IL-4: ↑, IL-10: ↑, BMP-2: ↑, VEGF: ↑, p-ERK: ↓, p-p38: ↓ | (Yang et al., 2019) |
| Bone marrow macrophages treated with M-CSF and RANKL | Li-SLA coated titanium disc | Oc.N: ↓ | (Huang et al., 2019) |
| Bone marrow macrophages treated with M-CSF and RANKL | LiCl (0.2–5 mM) | Oc.N: ↓, area of osteoclast per well: ↓, bone resorption area: ↓, CTSK: ↓, Oscar: ↓, Sema-4A: ↓, p-GSK3β: ↑, p-Akt: ↔, p-ERK: ↔, p-p38: ↔, p-JNK: ↔, p-IκBα: ↓, p-p65: ↓, c-Fos: ↓, NFATc1: ↓ | (Hu et al., 2017) |
| Foetal long bones stimulated for resorption by PTH, PGE2, IL-1 or 1,25(OH)2D3 | Lithium (3 mM) | No effect on basal resorption and resorption stimulated by IL-1; slight and inconsistent inhibitory effect on resorption stimulated by PTH; moderate and inconsistent inhibitory effect on resorption stimulated by PGE2; complete inhibition of resorption by 1,25(OH)2D3. | (Pepersack et al., 1994) |