Microvibration stimulates β-catenin expression and promotes osteogenic differentiation in osteoblasts

Nuclear envelope mechanobiology: linking the nuclear structure and function

“…While one aspect of SUN protein effects is centered around microtubule regulation of proliferation, SUN proteins also regulate mechanical response. Mechanical stimulation via low-intensity vibration (LIV), strain, and ECM activates mechanically sensitive biomolecular pathways such as Yes-associated-protein (YAP) and β-catenin /Wnt pathways [6,13,18,51,52], that in turn regulate both proliferation and differentiation [18,37,51,[53][54][55][56][57].…”

“…SUN proteins regulate mechanical response to strain and atomic force microscopy-induced cell deformation by restricting YAP [58] and β-catenin [16,59] entry into the nucleus by disrupting nuclear pore complex organization [60,61]. Additionally, SUN proteins are required for mechanoresponse and mechanoregulation of adipogensis in MSCs [37, [53][54][55][56] during low-intensity vibration (LIV). Interestingly, de-coupling of nesprins and SUN proteins also inhibits mechanoresponse to LIV [37, [53][54][55][56].…”

“…Additionally, SUN proteins are required for mechanoresponse and mechanoregulation of adipogensis in MSCs [37, [53][54][55][56] during low-intensity vibration (LIV). Interestingly, de-coupling of nesprins and SUN proteins also inhibits mechanoresponse to LIV [37, [53][54][55][56]. Decoupling of the LINC complex also decreases nuclear strain and deformation during microneedle manipulation indicating physical force transmission from the cytoskeleton into the nucleus is lost during loss of function of the LINC complex [48].…”

“…Additionally, isolated nuclei lose their ability to stiffen during magnetic bead displacement pulling on nesprin-1 during simultaneous SUN1 and SUN2 depletion [62]. However, strain can overcome the depletion of SUN proteins and decoupling of the LINC complex activating mechanosensitive pathways located at the focal adhesions and cytoskelton [37,48,[53][54][55][56]. It is clear that the LINC complex is important for cellular functioning and mechanoreponsiveness, and is the lynchpin by which mechanical and biomolecular signals enter the nucleus.…”

“…While emerin regulates the physical connection of the nucleus to the cytoskeleton, its role has redundancy with that of the LINC complex. During LIV, depletion of emerin in MSCs does not impede mechanoactivation of the focal adhesions [37, [53][54][55][56]. However, emerin has been shown to have a major impact on chromatin organization.…”