Mechanical Loading Regulates NFATc1 and -Catenin Signaling through a GSK3 Control Node*

Mechanical stimulation can prevent adipogenic and im-prove osteogenic lineage allocation of mesenchymal stem cells (MSC), an effect associated with the preservation of -catenin levels. We asked whether mechanical up-regula-tion of -catenin was critical to reduction in adipogenesis as well as other mechanical events inducing alternate MSC line-age selection. In MSC cultured under strong adipogenic condi-tions, mechanical load (3600 cycles/day, 2 % strain) inactivated GSK3 in a Wnt-independent fashion. Small interfering RNA targeting GSK3 prevented both strain-induced induction of -catenin and an increase in COX2, a factor associated with increased osteoprogenitor phenotype. Small interfering RNA knockdown of -catenin blocked mechanical reduction of peroxisome proliferator-activated receptor and adiponec-tin, implicating -catenin in strain inhibition of adipogene