Table 1.

Mechanotransduction elements involved in osteoblastic differentiation of MSCs.

Protein	Outcome	References
Focal adhesions	- Act as signaling relays for mechanotransduction by recruiting vinculin, paxilin and talin as well as signaling molecules including FAK, Src, and Akt. - Subset of focal adhesions directly connect to nuclear envelope - Depletion of Sun and Nesprin proteins of LINC complex change focal adhesion dynamics and size- Provide a physical coupling between extracellular matrix and cytoskeleton.	[113–117,156–159]
RhoA/Rock	- Regulates the actin cytoskeleton contractility. - LINC-cytoskeleton coupling regulates RhoA-GTPase levels - Inside the nucleus increases SP7 and Runx2 expression - Overexpression increases osteoblastogenesis- Deactivation leads to reduced osteogenesis	[118–121,154,160]
FAK	- FAK activation initiates the Akt mediated inhibition of GSK3β function leading to increased levels of β-catenin and its nuclear accumulation	[127,128]
YAP/TAZ	- YAP and TAZ nuclear entry are triggered by soluble or mechanical factors that increase F-actin contractility, proliferation and differentiation into osteoblastic lineage. - YAP/TAZ nuclear entry is in-part depends on LINC complex function. - Depletion of YAP/TAZ decreases bone quality.	[61,129–137,140,141]
βcatenin	- βcatenin nuclear envelope association and nuclear entry are in-part dependent on LINC complex function. - Wnt activated βcatenin/TCF1 complex binds and activates Runx2 expression in MSCs. - Increases cell proliferation and preserves multipotentiality by suppressing osteogenic gene loci through regulation of enhancer of zeste homolog 2, a key component of the polycomb repressive complex 2 in MSCs - Single allele deletion in osteocytes mutes bone anabolic response to loading- Promotes bone formation in osteoblasts	[62,138,139,166,145,146]
Lamin A/C	- Lamin A/C levels increase during osteogenesis - Correlates with tissue stiffness and depletion leads to decreased osteoblastogenesis- Overexpression accelerates osteoblastogenesis. - Lmna − /− mice have significantly reduced bone mass and deteriorated microarchitecture.	[174–180]
Torsin A	- Functional role in the formation of perinuclear actin cables during rearward nuclear movement suggests that it is important in regulating the cytoskeletal dynamics at the nuclear envelope	[183–187]
Nuclear F- actin	Nuclear F-actin increases osteogenic differentiation, this effect is blocked by depleting nuclear formin mDia2 or by CK666, an actin branching inhibitor.	[143,194,195]
Emerin	Recruits non-muscle myosin IIA to promote local actin polymerization and regulates nuclear export of βcatenin.	[188–193]