Table 1.
In vitro studies.
| Type of Wear Particles | Cell Type | Evaluations | Results: Osteolysis vs. Control | Ref. |
|---|---|---|---|---|
| 100 mg/mL Ti alloy particles (ø < 8 µm) | Raw 264.7 | Gene expression (Tnf) Protein levels (TNFα, p-TAK1, TAK1, p-P38, p-38, cytosolic and nuclear p50 and p65) | ↑ TAK1, Tnf, TNFα, nuclear and cytosolic p50, nuclear p65, p-38 | [32] |
| 1 mg/mL ZrO2 or Ti alloy particles (ø 5 µm) | Mice peritoneal macrophages | Gene expression (Tlr2, Tlr3, Tlr4, Tlr9, Myd88, Ticam2, Tnfrsf11a, Tnf, Il1, Il6) Protein levels (IL1β, IL6, TNFα) | ↑ Tlr2, Tlr3, Tlr4, Tlr9, MyD88, Ticam2, Nfκb, Tnf, Il1, Il6, TNFα. ↑ Tlr2, Tlr9; ↓ Tlr3, Tlr4, MyD88, Ticam2, Nfκb, Tnf, Il1, Il6 in ZrO2 than Ti | [54] |
| 0.05, 0.5, 1 mg/mL Ti alloy particles (ø 0.52 µm) | SFs from OA pz | Protein levels (IRE1-α, CHOP, RANKL, OPG, sRANKL) Gene expression (TNFSF11, TNFRSF11B) OCs number | ↑ CHOP, TNFSF11, RANKL, sRANKL, IRE1α (dose-dependent manner) | [53] |
| 0.1 mg/mL Ti particles (ø < 10 µm) | RAW264.7 | Cell viability Gene expression (Tnf, Il1, Il6, Il10, Ccl2, Ccl3, Nos2, Cox2) Protein levels (TNFα, IL1β, IL6, IL10, MCP-1, MIP-1α, iNOS, COX2) | ↑ Tnf, Il1, Il6, Il10, Ccl2, Ccl3, Nos2, Cox2, TNFα, IL1β, IL6, MCP1, MIP1α, iNOS, COX2 ↓ IL10 | [29] |
| 0.1 mg/mL Ti particles (ø 2.6 mm) | Raw264.7 | NO production Intracellular ROS Lipid peroxidation Gene expression (Nos2, Nox1, Nox2, Sod1, Nos3, Gpx, Gr, Catk, Tnf, Nfκb) SOD, CAT, GR activities Protein levels (TNFα, p-NFκB -p65, NFκB-p65) | ↑ NO, ROS, Nos2, Nox1, Nox2, Tnf, Nfκb, TNFα, p- NFκB -p65, GR, SOD, CAT ↓ Sod1, Nos3, Gpx | [30] |
| 0.1 mg/mL Ti particles (ø 4.5 µm) | RAW264.7 | CB2 activity Bone resorption pit assay OCs number Protein levels (IL1β, TNFα) Gene expression (Cnr2, Tnfrsf11a, Ctsk) | ↑ OCs number, Cnr2, Tnfrsf11a, Ctsk, TNFα, IL1β, CB2 activity, resorption area | [31] |
| 0.1 mg/mL Ti particles (ø 4.50 µm) | RAW264.7 | Protein levels (IL1β, TNFα) Gene expression (Il1, Tnf) | ↑ Il1, Tnf, IL1β, TNFα | [33] |
| Calvaria with CM of RAW264.7 stimulated with 1 mg/mL Ti particles RAW264.7 with 1% Ti particles (ø < 3.6 µm) | Calvaria from mice (5-day old) and RAW264.7 | OCs number Gene expression (Trap, Cstk, Calcr, Nfκb, Tnf, Il1, Il6, Cox2, Nos2) Protein levels (TNFα, IL1β, IL6, cytosol and nuclear p65) | Calvaria: ↑ OCs number, Trap, Cstk, Calcr, Nfκb. RAW264.7: ↑ Tnf, Il1, Il6, Cox2, Nos2, NOS2, IL1β, IL6, TNFα, nucleus p65; ↓ cytosol p65 | [4] |
| 4x104–4x106 particles/mL TiO2-N (ø <0.1 µm) or TiO2-M (ø <5 µm) | THP-1 | Protein levels (TNFα, IL-10) Gene expression (TNF, IL10, CXCL10, CCR7, MRC1) | TiO2-M: ↑ TNFα, IL-10, TNF, IL10, CXCL10, CCR7 (at the highest concentration) | [45] |
| 0.1 mg/mL Ti particles (ø 3.6 µm) | Mice BMM | OCs number Bone resorption assay Gene expression (Ctsk, Trap, Nfatc1, Mmp9, Il1, Il6, Tnf) Protein levels (TNFα, IL1β, IL6) | ↑ OCs number, Trap, Nfatc1, Ctsk, Mmp9, Tnf, Il1, Il6, TNFα, IL1β, IL6, resorbed area | [50] |
| TiO2 (ø 8 nm) | RAW264.7 | Cell viability Gene expression (Tnf, Il1, Cxcl2, Ccl2, Vegfa, Pdgfa) | ↓ cell viability, Cxcl2, ↑ Ccl2 | [6] |
| 2.5 mg/mL Ti particles (ø 4.5 µm) | MC3T3-E1 | Gene expression (Cnr2, Tnfrsf11b, Tnfsf11) Caspase-3 activity Protein level (CB2, ALP, OCN, COLL I); Cell viability Apoptosis Mineralization | ↑ Cnr2, CB2, apoptosis, caspase-3 activity, Tnfsf11 ↓ cell viability, ALP, COLL I, OCN, mineralization, Tnfrsf11b/Tnfsf11 | [38] |
| 0.05% (v/v) Ti particles (ø 0.3–1 µm) | MC3T3-E1, RAW264.7, mice primary OBs and BMMs | Gene expression (Il6, Cox2, Il1, Tnf, Fam213A) Protein levels (p-ERK) Cell membrane damage and death | MC3T3-E1:↑ Il6, Cox2, Fam213A, membrane damage ↓ viability. RAW264.7: ↑ Il6, Cox2, Tnf, Il1 membrane damage ↓ viability OBs, BMMs: ↑ Il6, Cox2, Fam213A, Il1, Tnf, p-ERK | [28] |
| 0.1 mg/mL Ti particles (ø < 10000 µm) | MC3T3-E1, RAW264.7 | Gene expression (Tnf, Il6, Il1, Trap, Nfatc1, Csf1, Tnfsf11, Tnfrsf11b) Protein levels (TNFα, NFATc1, BMP2) Cell viability OCs number; Bone pit resorption assay | RAW264.7: ↑ Tnf, Il6, Il1, Nfatc1, NFATc1, OCs number, resorbed area. MC3T3-E1: ↑ Tnfsf11, Il6 | [27] |
| Ti particles (ø 1–3 µm) | MC3T3-E1, hMSCs | Protein levels (p-p44; p-p42, pCREBβ, IL6, PGE2) Gene expression (Il6, Cox2) OCs number | ↑ Il6, Cox2, p-ERK, pCREBPb, IL6, PGE2, OCs number | [39] |
| 2.5 mg/mL Ti particles (ø < 4 µm) | Saos-2, OBs from pz | Cell viability Protein levels (IL6) Gene expression (Il6) | ↑ IL6, Il6 | [40] |
| 100 particles/cell TiO2 particles (ø 0.43 µm) | hMSC from OA pz | ALP activity Mineralization Cell viability Protein levels (IL6, IL8) Gene expression (TNFRSF11B, BCL10, COMP, FGFR2, IGF1, BMP6, SOX9, COLLs, CSF2, BAD, CD70, BCL2) | ↓ cell viability, ALP activity, mineralization, TNFRSF11B, BCL10, COMP, FGFR2, IGF1, BMP6, SOX9, COLLs; ↑ CSF2, BAD, CD70, BCL2 | [52] |
| 0.1 mg/mL Ti (ø 4.5 µm) or PMMA particles (ø 6 µm) | Mice BMM | Phagocytosis OCs number Gene expression (Nfatc1, Trap, Mmp9, CtsK, Calcr) Bone pit resorption assay Protein levels (TNFα, NFATc1) | ↑ OCs number, Nfatc1, Trap, Mmp9, Ctsk, Calcr, resorbed area, TNFα, NFATc1, phagocytosis | [49] |
| 1:100 (cells: particles) Ti or CE particles (ø 0.2 or 1.2 µm) | RAW264.7 | Gene expression (Pik3cb, Pik3r2, Tnf) Protein levels (TNFα, p-AKT) | ↑ Pik3cb, Tnf, TNFα, p-AKT | [34] |
| 5 mg/mL UHMWPE particles (ø 2.6 µm) | RAW264.7 alone or co-cultured with DC2.4 | OCs number Protein levels (TNFα, MCP-1, p65, p-p65) Gene expression (Mmp9, Calcr, Cstk) | Raw264.7: ↑ OCs number, TNFα, MCP-1, p-p65, p65, Mmp9, Ctsk, Calcr. Co-cultures: ↑ OCs number, MCP-1, p-p65, p65, Mmp9, Ctsk, Calcr | [35] |
| 0.5 or 0.75 mg/mL UHMWPE particles (ø < 9 µm) | RAW264.7 | DNA quantification Live/Dead Gene expression (Nfatc1, Tnfrsf11a, Tnfsf11, Tnfrsf11b) Pit resorption assay Protein levels (RANKL, OPG, TNFα, PGE2) NFκB assay | ↓ DNA quantification (at 3 days) ↑ Tnfrsf11a (at 7 days), Tnfsf11 (at 3 days), RANKL, TNFα, PGE2, NFκB activation ↑ Tnfsf11a (at 3 days), Nfatc1, RANKL, resorption activity in 0.75mg/mL PE than 0.5 mg/mL | [37] |
| 1:100 or 1:500 (cells: particles) UHMWPE particles (ø 1.74 µm) | MG-63 | Gene expression (TNFSF11, TNFRSF11B) Protein levels (RANKL, OPG) ALP activity | ↑ RANKL, TNFSF11 ↓ ALP activity. ↑ TNFSF11; ↑ TNFRSF11B, ALP activity in 1:500 than 1:100 | [43] |
| 1:100 or 1:500 (cells: particles) UHMWPE particles (ø 1.74 µm) | Primary hOBs from fractured pz | Gene expression (TNFRSF11B, TNFSF11) Protein levels (RANKL, OPG) ALP activity | ↑ TNFSF11, RANKL ↓ ALP activity ↑ TNFSF11 in 1:500 more than 1:100 | [48] |
| 1:100 or 1:500 (cells: particles) UHMWPE particles (ø 1.74 µm) | THP-1 | Gene expression (TNFRSF11A, TNF) Protein levels (RANK, TNFα, IL1β, IL6, CGRPR1) | ↑ CGRPR1, TNFα, IL1β, IL6, TNF ↑ IL1β, TNFα, TNF, IL6 in 1:500 more than 1:100 | [20] |
| 1 mg/mL UHMWPE, HA particles (ø 10 µm) | ROS 17/2.8 | Protein levels (TNFα, RANKL, OPG) Gene expression (Tnfrsf11b, Tnfsf11) | UHMWPE: ↑ TNFα ↓ OPG, Tnfrsf11b. HA: ↑ TNFα, OPG, Tnfrsf11b | [44] |
| 10 mg/mL HDP particles (ø 8.59 µm) | Primary FBs from the subcutaneous tissues of cranial capsules of mice, OBs from mice | Protein levels (IL6) Gene expression (Tnfsf11, Tnfrsf11b, Il6, Il1, Tnf, Cox2) | FBs: ↑ IL6, Il6 | [47] |
| 5 mg/mL PMMA particles (ø 0.33 µm) | RAW264.7 | TRAP function OCs number Gene expression (Ctsk, Trap, Tnfrsf11a, Cys1) | ↑ TRAP function, OCs number, Trap, Ctsk, Tnfrsf11a | [36] |
| 2 mg/mL PMMA particles (ø 0.1–10 µm) | Rat BMM | Gene expression (Il1, MhcII, Il10, Tgfb1, Ccr2) Protein levels (iNOS) | ↑ Il1, MhcII, Il10, Tgfb1, Ccr2, iNOS | [51] |
| 1 mg/mL PMMA particles (ø 6 mm) | MC3T3-E1 | Cell viability LDH ALP activity; Gene expression (Nfκb, Runx2, Sp7, Bglap) | ↑ LDH, Nfκb ↓ cell viability, ALP activity, Runx2, Sp7, Bglap | [41] |
| 0.3 or 2.5 mg/mL Co-Cr alloy particles (ø 5.7 µm); 62 or 500 µm Co (II) or Cr (III) (ø < 0.2 µm) | MC3T3-E1 | Cell viability ALP activity Gene expression (Ccl2, Tnf, Il6, Tnfsf11, Tnfrsf11b, Nfatc1, Runx2, Sp7, Lrp5) | Co-Cr alloy: ↓ cell viability, ALP activity, Runx2, Sp7 ↑ Nfatc1, Tnf, Il6, Ccl2 (dose-dependent manner). Co(II): ↓ cell viability, ALP activity, Tnfrsf11b, Lrp5, Runx2, Sp7 ↑ Tnfsf11, Tnf, Nfatc1 (dose-dependent manner). Co-Cr alloy: ↑ Ccl2, Tnf, Nfatc1 than Co(II) | [40] |
| 1 mg/mL Co-Ni-Cr-Mo-alloy or Co-Cr-Mo-alloy (ø < 5 µm) | MG-63, Saos-2 | Gene expression (CXCR4, TNF) Protein levels (CXCR4) | ↑ CXCR4, CXCR4, TNF. ↓ CXCR4, CXCR4, TNF in Co-Ni-Cr-Mo more than Co-Cr-Mo | [1] |
| 1:10, 1:100, 1:200, 1:500, 1:1000 (cells: particles) Co-Cr-Mo alloy from THA femoral head (ø 0.81 µm) | THP-1 | Cell viability Cytosol and nuclear protein levels (I-KB, NFκB, IL1β, TNFα, IL8) Gene expression (Il8) | ↑ IL1β (at 1:1000), IL8, Il8 (at ≥1:500), nuclear NFκB ↓ cytosolic I-KB, cytosolic NFκB, cell viability (at 1:1000) | [46] |