Table III.
Details of mechanical loading models
| Study | Status of force | Loading methods | Magnitude | Loading time | Related molecules |
|---|---|---|---|---|---|
| Compressive force | |||||
| Studies investigating osteoclastogenesis | |||||
| Asano et al6 (2011) | Static | Uniform compression method (Nakajima et al33 (2008)): by a glass cylinder with lead granules in a 90 mm dish | 1.0, 2.0, 3.0, 4.0 g/cm2 | 3, 6, 9, 12, 24 hrs | IL-8, MCP-1, TRAP staining; pit formation assay |
| Cao et al7 (2014) | Static | Uniform method (Mitsui et al34 (2005)): layer of glass with additional metal weights | 0.5, 1.0, 1.5, 2.0 g/cm2 | 2, 4, 6, 8, 12 hrs | Adrb2, RANKL, OPG, TRAP staining |
| Jin et al12 (2015) | Static | Uniform compression method (Kanzaki et al13 (2002); Nakajima et al33 (2008)): cover glass and glass bottle with lead granules | 2.0 g/cm2 | 0.5, 3, 6, 12 hrs | Piezo 1, RANKL, OPG, PGE2, COX-2, NF-κB, histone 3, TRAP staining |
| Kanzaki et al13 (2002) | Static | Uniform compression method: glass cylinder with lead granules | 0.5, 1.0, 2.0, 3.0 g/cm2 | 0.5, 1.5, 6, 24, 48 hrs | PGE2, COX-1, COX-2, RANKL, OPG, TRAP staining |
| Kikuta et al15 (2015) | Static | Uniform compression method (Nakajima et al33 (2008)) | 4.0 g/cm2 | 1, 3, 6, 9, 12, 24 hrs | Jagged1 (Notch signalling), RANKL, sRANKL, IL-6, TRAP staining; pit formation assay |
| Kook et al17 (2011) | - | FX-4000 Compression System | 0.5% elongation (compression) | 1, 3, 6, 24 hrs | OPG, RANKL, TNF-α, TRAP staining; bone resorption assay |
| Kunii et al18 (2013) | Static | Uniform weight method (Yamaguchi et al29 (2006)) | 1.0, 2.0, 4.0 g/cm2 | 3, 6, 8, 12, 24, 48, 72 hrs | IL-6; pit formation assay |
| Mayahara et al19 (2012) | Static | Cell layer covered by thin glass plate | 2.0 g/cm2 | 24 hrs | COX-2, RANKL, OPG, TRAP staining |
| Römer et al23 (2013) | Static | Glass cylinder upon cells (Kanzaki et al13 (2002)) | 2.0 g/cm2 | 24 hrs | PGE2, COX-2, RANKL, OPG, TRAP staining |
| Yamaguchi et al29 (2006) | Static | Uniform compression method (Kanzaki et al13 (2002)) | 0.5, 1.0, 1.5, 2.0, 3.0 g/cm2 | 3, 6, 9, 12, 24, 48 hrs | sRANKL, RANKL, OPG, TRAP staining; pit formation assay |
| Yoshino et al31 (2014) | Static | Uniform compression method (Yamaguchi et al29 (2006)) | 4.0 g/cm2 | 1, 3, 6, 9, 12, 24, 48 hrs | RANKL, sRANKL, TNF-α, TRAP staining; pit formation assay |
| Centrifugal force | |||||
| Studies investigating osteoclastogenesis | |||||
| Kook et al (2009)16 | - | Centrifugation: horizontal microplate rotor (Universal 32 R, Hettich, Germany) | 50 g/cm2 | 30, 60, 90 mins | RANKL, OPG, ERK1/2, p-ERK1/2, TRAP staining; bone resorption assay |
| Studies investigating osteogenesis | |||||
| Ueda et al27 (2016) | - | Centrifugation (Redlich et al35 (1998)) | 40, 90, 135, and 160 × g corresponded to 16.0, 36.0, 53.9, and 63.9 g/cm2 | 24 hrs | Asporin (ASPN), sclerostin (SOST), bone formation assay (Von Kossa staining) |
| Ueda et al28 (2016) | - | Centrifugation (Redlich et al35 (1998)) | 40 and 90 × g corresponded to 16.1 and 36.2 g/cm2 | 24 hrs | SOST/sclerostin, Von Kossa staining for mineralization |
| Tensile force | |||||
| Studies investigating osteogenesis | |||||
| Chang et al8 (2017) | Cyclic | Custom-made strain device Tension Plus System (Chang et al36 (2015)) | 12% elongation at 0.1 Hz (5 sec stretch, 5 sec relaxation) | 24, 48, 72 hrs | MicroRNA-195-5p, Wnt, FGF2, BMP ALP assay; Alizarin red staining |
| Chen et al9 (2014) | - | Tension incubator (TI, Model 3618P; Lab-Line Instruments, Inc., Thermolyne Co., Melrose Park, Illinois) Normal incubator as controls: 101.3 kPa | -100 kPa (1 Pa = 10-5 kg/cm2, equal to a negative force of 101 g/mm2) | 3, 6, 12, 24 hrs; 1, 3, 7, 15 days | FAK, ERK1/2, p-FAK, p-ERK1/2, COL, ALP, OCN, IL-1, TNF-α, ALP assay; Alizarin red staining |
| Diercke et al10 (2011) | Continuous | Method described by Hasegawa et al37 (1985): cells are seeded on flexible bottomed dishes, on top of which is placed a lead weight, causing the dish bottom and attached cells to be stretched | 2.5 % | 5, 15, 30 mins; 1, 4, 24, 48, 72 hrs | FAK, p-FAK, ERK1/2, p-ERK1/2, ephrinB2, EphB4, Alizarin red staining |
| Fujihara et al11 (2010) | Cyclic | Stretch apparatus Scholertec NS-350 (Scholertec, Osaka, Japan) | 110% elongation (30 cycles/min; 0.5 Hz) | 24, 48 hrs | DNA chip analysis, c-Fos, Runx2, ALP Glutamate signalling, ALP activity; Alizarin red Staining |
| Monnouchi et al20 (2015) | Cyclic uniaxial | STB-140 (STREX Inc., Osaka, Japan) | 8% elongation (0.5 sec stretch and 0.5 sec relaxation per cycle) | 1 hr | IL-11, Ang II pathway, Alizarin red staining |
| Ren et al22 (2015) | Cyclic | Flexcell FX-4000 Strain Unit (Flexcell International Corp., Hillsborough, North Carolina) | 10% deformation at 0.5 Hz (30 cycles/min) | 1, 3, 6, 12, 18, 24 hrs | Runx2, ATF4, SP7, OCN, BSP, ERK, p-ERK; Alizarin red staining |
| Sun et al24 (2016) | Cyclic intermittent | FX-5000T Flexcell Tension Plus unit (Flexcell) | 12% elongation at 0.5 Hz | 4 hrs per day for 1 and 5 days | IL-1β, TNF- α, Runx2, COL1, ALP activity; Alizarin red staining |
| Sun et al25 (2017) | Cyclic | FX-5000T Flexcell Tension Plus unit (Flexcell) | 12% elongation at 0.5 Hz | 12, 24, 48 hrs | IL-1β, TNF- α, Runx2, COL1, ALP activity; Mineralization assay |
| Yang et al30 (2016) | Cyclic | Flexcell FX-5000 Tension System (Flexcell) | 10% deformation at 0.5 Hz (30 cycles/min) | 1, 3, 6, 12, 24 hrs | ATF4, OCN, BSP ERS-related genes: Bip, Xbp1, PERK, eIF2α; Alizarin red staining |
| Studies investigating osteoclastogenesis | |||||
| Kanzaki et al14 (2006) | Cyclic | Flexercell Strain Unit (Flexcell) | 15% elongation (1 sec stretch/1 sec relaxation) | 0.5, 1.5, 6, 24, 48, 72 hrs | RANKL, OPG, TGF-β1, TRAP staining; pit formation assay |
| Kook et al17 (2011) | Cyclic | FX-4000 Tension System | 1.5% elongation | 1, 3, 6, 24 hrs | OPG, RANKL, TNF-α, TRAP staining; bone resorption assay |
| Fluid shear stress | |||||
| Studies investigating osteogenesis | |||||
| Qi and Zhang21 (2014) | - | Parallel-plate flow chamber using a closed loop | 3, 6, 9, 12, and 15 dynes/cm2 | 6 hrs | microRNA assay; ALP activity; mineralization assay, miRNA-132, ALP, OCN, OPN, PON, PI3K, Akt1, mTOR |
| Tang et al26 (2014) | - | A parallel-plate flow system | 12 dynes/cm2 | 15, 30, 60 mins; 6, 12, 24, 48 hrs; 7, 14, 21 days | COLI, ALP, Runx2, SP7, BMP2, p38, ERK1/2, ALP activity; calcium deposition (Alizarin red staining) |
IL, interleukin; MCP-1, monocyte chemotactic protein; TRAP, tartrate-resistant acid phosphatase; Adrb2, β-2 adrenergic receptor; RANKL, receptor activator of nuclear factor kappa-B ligand; OPG, osteoprotegerin; PGE2, prostaglandin E2; COX-2, cyclooxygenase-2; NF-κB, nuclear factor-κB; TNF-α, tumour necrosis factor-α; sRANKL, soluble RANKL; ERK1/2, extracellular signal-regulated kinase 1/2; p-ERK1/2, phospho-ERK1/2; FGF2, fibroblast growth factors; BMP, bone morphogenetic proteins; ALP, alkaline phosphatase; FAK, focal adhesion kinase; p-FAK, phospho-FAK; COL, collagen; OCN, osteocalcin; Runx2, runt-related transcription factor 2; Ang II, angiotensin II; ATF4, activating transcription factor 4; SP7, osteriox; BSP, sialoprotein; ERS, endoplasmic reticulum stress; Bip, binding immunoglobulin protein; Xbp1, X-box binding protein 1; PERK, protein kinase R like endoplasmic reticulum kinase; eIF2α, α-subunit of eukaryotic initiation factor 2; TGF-β1, transforming growth factor-β1; OPN, osteopontin; PON, periostin; PI3K, phosphoinositide 3-kinase; mTOR, mechanistic target of rapamycin