Table 3.

Overview of Hh signalling-related studies into the role of mechanical cues in mediating cellular function and fate.

Mechanical Factor		Model	Cell Response	Reference
Strain	Cyclic stretch	Human ligamentum flavum cells obtained by a tissue explant method	•Increased expression of IHH, SMO, GLI1, GLI2 and GLI3 and markers of osteogenesis •Increased ALP activity	[157]
	Cyclic strain and pulsatile flow	Adult rat vascular smooth muscle cells	Hh expression reduced by mechanical stimulation: •Decreased proliferation and increased apoptosis. •Decreased expression of Shh and Ptch1	[247]
	Cyclic tensile strain	Primary bovine articular chondrocytes and chondrocyte cell line (from Tg737ORPK mice)	•Mechanical strain upregulates Ihh expression. •Increased expression of Gli1 and Ptch1	[161]
Compression	Hydrostatic loading	Primary rat epiphyseal chondrocytes	Increased Ihh gene expression and Ihh-responsive GLI-luciferase activity. This was obstructed by disrupting primary cilia structure.	[248]
	Static pressure	Rabbit condylar chondrocytes	Increased expression of COL2A1, SOX9, ALP, Runx2, and increased mRNA levels of Ihh and PTHrP	[249]
Shear Stress	Oscillatory fluid flow	Murine C3H10T1/2 ​cell line	•Increased expression of Ptch1, Gli1, Runx2 and Opn. •Enhanced osteogenesis via a Gpr161, AC6, cAMP, Hh mechanism.	[158]
Elasticity	Methacrylated gelatin hydrogels	Murine embryonic fibroblasts	Varying expression of Gli1 and β1-integrin with varying hydrogel stiffness.	[162]
Topography	Titanium discs with pits (ranging from 1 to 40 ​μm) and nanotubes of diameters 25 & 70 ​nm	Human MG63 (osteoblastic) cell line	Increased expression of Smo, Gli1, Shh on textured surfaces.	[159]

Abbreviations: RUNX2, Runt-related transcription factor 2; OSX, Osterix; ALP, alkaline phosphatase; OCN, Osteocalcin; OPN, Osteopontin; Shh, Sonic hedgehog; Ihh, indian hedgehog; SMO, Smoothened; Gli1, glioma-associated oncogene homolog 1; Gli2, glioma-associated oncogene homolog 2; Gli3, glioma-associated oncogene homolog 3; RANKL, receptor activator of nuclear factor-κB ligand; COL2A1, collagen type II alpha-1 chain; μm, micrometre; nm, nanometre.