TABLE 1.
Summary table for in vitro studies on osteocytes in response to mechanical stimulations. Abbreviations: Sclerostin (Sost), cyclooxygenase-1 (COX-1), osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), podoplanin (E11), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), connexin 43 (Cx43), matrix extracellular phosphoglycoprotein (Mepe), phosphate regulating endopeptidase homologue, X-linked (Phex), dentin matrix protein 1 (Dmp1).
| Cell type | Mechanical stimulation | Gene/Protein expression | Outcome |
|---|---|---|---|
| Osteocyte cell lines | |||
| MLO-Y4 | Oscillatory fluid flow, 1 Pa/2 h | COX-2, RANKL/ OPG | Response of integrin β1 under oscillatory fluid flow. The absence of β1 showed a reduction in COX-2 and PGE2 (Litzenberger et al., 2010) |
| MLO-Y4 | Oscillatory fluid flow, 1 Pa/2 h | COX-2, Runx-2, integrin αVβ3, E11 | Increased expression of integrin-associated molecules including vinculin, osteopontin, and CD44. Also, more cell spread and fiber stress are formed by fluid flow (Xu et al., 2012; Zhang et al., 2015) |
| MLO-Y4 | Oscillatory fluid flow, 0.5–5 Pa/1–4 Pa | COX-2, RANKL/ OPG | Cells were exposed to different shear stress amplitude (0.5–5 Pa), oscillating frequency (0.5–2 Hz), and duration (1–4 h). COX-2 Upregulated gene expression levels for COX-2 response to higher shear stress amplitudes, faster oscillating frequencies, and longer flow durations, which direct towards bone formation (Li et al., 2012) |
| MLO-Y4 | Fluid shear stress, 16 Pa/0.5–2 h | OPG, Cx43, PGE2 | Fluid shear stress induces the opening of Cx43 and redistributes Cx43 protein, which promotes PGE2 release (Chen and Sambrook, 2001; Cherian et al., 2005) |
| MLO-Y4 | Pulsating fluid flow, 0.7 Pa/1 h | Mepe, RANKL/OPG | Pulsatile fluid flow induced Mepe, but not Phex. RANKL/OPG gene expression decreased (Kulkarni et al., 2010) |
| Ocy454 | 3D fluid shear stress, 0.5–2.0 Pa/2 h or 3 days | Sost, Dmp1, RANKL, OPG, Phex, Mepe, Osteocalcin | Long-term fluid shear stress (3 days) in 2D LS increases Sost, Dmp1, RANKL, OPG, Phex, Mepe (Spatz et al., 2015; Wein et al., 2015) |
| Ocy454 | Laminar fluid flow, 0.8 Pa/45 min | Sost | Laminar fluid flow downregulated Sost gene expression and demonstrated HDAC5 is required for loading-induced Sost suppression (Sato et al., 2020) |
| Primary osteocytes | |||
| Chicken osteocytes | Pulsating fluid flow, 0.5 Pa/1 h, 0.7 Pa/10 min | PGE2 | Osteocytes rapidly respond to fluid flow to increase PEG2 (Ajubi et al., 1996) |
| Intracellular Ca2+ level was increased through mechanosensitive ion channels (Ajubi et al., 1999) | |||
| Mouse calvariae | Pulsating fluid flow, 0.7 Pa/1 h | PGHS-2 (Prostaglandin G/H synthase), PGE2 | After pulsating fluid flow, osteocyte s upregulated PGHS-2 gene expression, leading to more conversion of arachidonic acid into PGE2 (Klein-Nulend et al., 1997) |
| Human calvarial cells/biopsies | Pulsating fluid flow, 0.7 Pa/1h | PGE2, COX-2, Nitric oxide | Pulsating fluid flow upregulated PGE2, COX-2, but not COX-1 gene expression (Sterck et al., 1998; Klein-Nulend et al., 1998; Joldersma et al., 2000) |