Table 1. Review of osteoblastic responses to various flow patterns.

Flow types/Shear stress details	Responses	Year	Reference
Unidirectional steady flow
4.3dyn/cm2, 0.5-15min	cAMP increased up to 12 fold, which was mediated by prostaglandin.	1990	Reich [9]
6 or 24dyn/cm2, 5min-8 h	PGE2 increased 40% after 5 min and 9- to 20-fold in 8 h, higher shear resulted more increase. 24 dyn/cm2 increased IP3 up to 2 h and partially due to PKC activation and mediated by PGE2;	1991	Reich [31]
18, 35, 70dynes/cm2	[Ca2+]i responses (peak amplitude and number of responsive cells) increased in a manner dependent on FSS magnitude;	1995	Hung [12]
6dyn/cm2, up to 12h	NO (in NOS form) increased and sustained for 12 h;	1996	Johnson [45]
4dyn/cm2, up to 8h	ALP decreased compared with static control;	1997	Hillsley [41]
17–20dyn/cm2, up to 24h	mRNA and protein of TGF-β1 increased after 3 and 24 h via cation channel. No mRNA expression of PDGF-A, IGF-I, IGF-II, or IL-6 was detected;	1998	Sakai [46]
12dyn/cm2, 1h	Actin cytoskeleton Reorganization, recruitment of β1-integrins and α-actinin to focal adhesions, mRNA and protein of Cox-2 and c-fos was increased.	1998	Pavalko[15]
12dyn/cm2, up to 3h	The process required IP3-mediated [Ca2+]i release;	2000	Chen[22]
0.25-26dyn/cm2, up to 6h	Transient FSS associated with the onset of flow stimulated ∼ 4-fold increase in NO release compared with steady flow;	1999	McAllister [47]
10dyn/cm2, 24h	Increased IL-11 (mediated by prostaglandin) and stimulated bone remodeling;	1999	Sakai [48]
10dyn/cm2, 4 or 4.5h	Induction of Cox-2 expression was via a PKA, not PKC signaling pathway	2002	Wadhwa [49]
5 or 20dyn/cm2, 1-3h	Disrupted junctional protein distribution and decreased intercellular coupling	2003	Thi [34].
12dyn/cm2, 4 or 6h	Inhibited TNF-α induced apoptosis via PI3-kinase activation and caspase-3 inhibition;	2003	Pavalko[50]
20dyn/cm2, 30min	Increased proliferation, ALP activity, phosphorylation of ERK and expression of integrin-β1, which may involve ERK, NO synthase, Cox, and PTX pathway; NF-κB translocation was essential for shear induced Cox-2 increase, which	2003	Kapur [39]
12dyn/cm2, up to 2h	was dependent on [Ca2+]i release;	2003	Chen [51]
10dyn/cm2, 90min	The induction of Cox-2 and PGE release did not require intact microfilaments or microtubules;	2004	Norvell [42]
10dyn/cm2, 10min	Plasma membrane cholesterol was essential for mechanotransduction;	2004	Ferraro [52]
10dyn/cm2, up to 5h	Fibronectin-induced formation of focal adhesions promoted FSS-induced PGE2 release and upregulation of Cox-2 protein;	2004	Ponik [35]
1-63×10-5dyn/cm2, up to 48h	Increased proliferation, ALP, and fibronectin via stimulation of PEG2 and TGF-β1;	2004	Liegibel [53]
10dyn/cm2, 1h	Modulated the activity of GSK-3β and β-catenin, which regulated Cox-2 expression;	2004	Norvell [54]
12dyn/cm2, up to15min	Induced ATP release was Ca2+ dependent and mediated PGE2 release via P2 receptor activation [43];	2005	Genetos
10 or 20dyn/cm2, 2h	Increased cell stiffness;	2007	Jaasma [55]
pulsatile cycles (0.8-10dyn/cm2, 0.5Hz, 60s) and laminal flow (14min, 0.8dyn/cm2, 8 or 12h)	Increased collagen I and MMP-1, 3 gene expression depended on the integrity of microtubule but not on actin filaments;	2007	Myers [56]
12dyn/cm2, up to 60min	The induced ERK1/2 phosphorylation requires Ca2+-dependent ATP release, which was mediated through P2Y7, not P2Y2 [44];	2008	Liu D
12dyn/cm2, up to 24h	Integrin-β1 played predominant roles for shear-induced signaling and gene expression. Integrin-β1/Shc association led to the activation of ERK;	2008	Lee[57]
4, 8, 16dynes/cm2, 30min	Increased PGE2 was mediated by Cx43-hemichannel that adapted to mechanical loading;	2008	Siller-Jackson [58]
20dyn/cm2, 2h	Increased vimentin and cross-linking proteins (α-actinin and filamin);	2008	Jackson [36]
12dyn/cm2, up to 20min stepwise increasing/decreasing (5-10-15, or 15-10-5 dyn/cm2), 6 or 12 h	Type II cGMP-dependent protein kinase mediates mechanotransduction; RANKL/OPG ratio decreased with stepwise increasing stimulation and increased with decreasing shear. ALP and calcium deposition increased unless the step change was increased to 10dyn./cm2.	2009	Rangaswami [59] The present study
Pulsatile flow
0-15dyn/cm2(average5), rectified half sine wave, up to 24h	ALP mRNA decreased compared with static control and steady flow of 4 dyn/cm2, but no change in mRNA of collagen and osteopontin;	1996	Hillsley [41]
6±5dyn/cm2, 3Hz, up to 48h, (0.6, 6)±5dyn/cm2, 0.3Hz, 7days	PEG2 increased shortly, 7 days' increased proliferation, ALP but not mineralization compared with static control;	2001	Nauman [32]
12dyn/cm2, 1Hz, square wave, 15min	Proliferation increased more than the same level of steady flow (a smooth 30s ramped increase from 0 to 12 dyn/cm2, sustained steady shear for 7 min, and a smooth 30s ramped decrease 30s) via ERK1/2 and Rb protein;	2002	Jiang [61]
3.9 dyn/cm2 (3 Hz) or 6.4 dyn/cm2 (5 Hz), 10min	Increased alignment of stress fibers. The increased NO release was inhibited by disrupting actin while the increased PGE2 was inhibited by disrupting either the actin or microtubule [60];	2005	McGarry JG
10dyn/cm2, 5Hz, 30min	Cbfa1/Runx2 was necessary for maximal induction of Cox-2;	2006	Mehrotra [62]
10dyn/cm2, 5Hz, 1h	Sustained induction of RANKL expression after stopping FSS was dependent on PKA and ERK signaling pathways;	2006	Mehrotra [37]
5dyn/cm2, 1Hz, 5h	Upregulated vascular endothelial growth factor gene expression;	2007	Thi [63]
Oscillatory flow
20dyn/cm2, 0.5 or 1.0 or 2.0Hz, 4min	Increased [Ca2+]i and the response decreased with the increase of frequency. The [Ca2+]i response decreases in the order of pulsatile (0-2 Pa), steady (2 Pa) and oscillatory flow (+/-2Pa).	1998	Jacobs [16]
20dyn/cm2, 1Hz, up to 2h	[Ca2+]i released and OPN gene expression increased via ERK1/2 and p38 activation;	2001	You [64]
1.9, 4.7, 9.3dyn/cm2, 1Hz, 1- 2h	Inhibited TNF-α induced NF-κ B activation via an IKAPPA B kinase;	2001	Kurokouchi [65]
20dyn/cm2, 2Hz, up to 15min	Refractory periods between the [Ca2+]i oscillation. Multiple low-magnitude oscillations of [Ca2+]I existed during continuous flow.	2003	Donahue [66]
Up to 20dyn/cm2, 1Hz, up to 1h	Sufficient nutrient supply or waste removal is needed for the response to oscillating fluid flow induced shear stress;	2003	Donahue[67]
10 or 20dyn/cm2, 1Hz, up to 1h	Insertion of short-term rest periods resulted in multiple[Ca2+]i responses, increases in [Ca2+]i magnitudes and overall responding cells and OPN mRNA, but not PGE2;	2005	Batra [18]
10dyn/cm2, 1Hz, 1h	Decreased ratio of RANKL/OPG;	2006	Kim [29]
11dyn/cm2, 0.5Hz, 1, 5, 24h	Delayed in stress fiber formation and alignment, but similar temporal effects on induction of Cox-2 and OPN protein expression compared with unidirectional flow (8 dyn/cm2);	2007	Ponik [40]
10-12dyn/cm2, 0.5Hz, up to 4h	FAK was important for FSS-induced mechanotransduction;	2009	Young [68]
20dyn/cm2, 1Hz, sine wave, 2h	Gap junctions are involved in the mechanosignaling process.	2009	Jekir [69]