DEC1 deficiency results in accelerated osteopenia through enhanced DKK1 activity and attenuated PI3KCA/Akt/GSK3β signaling.

摘要: Abstract Background Human differentiated embryonic chondrocyte expressed gene 1 (DEC1) has been implicated in enhancing osteogenesis, a desirable outcome to counteract against deregulated bone formation such as retarded development, osteopenia and osteoporosis. Methods results DEC1 knockout (KO) the age-matched wild-type (WT) mice were tested for impact of deficiency on development function age. exhibited at age 4 weeks osteopenic phenotype both 4- 24-week old mice. However, was more severe groups. Mechanistically, downregulated expression bone-enhancing genes Runx2 β-catenin accompanied by upregulating DKK1, an inhibitor Wnt/β-catenin signaling pathway. Consistently, favored attenuation integrated PI3KCA/Akt/GSK3β signaling, pathway targeting degradation. Likewise, greater group. These changes, however, reversed vivo treatment with lithium chloride, stabilizer β-catenin, confirmed gain-of-function study transfection into KO marrow mesenchymal stem cells loss-of-function siDEC1 lentiviral infection corresponding WT cells. Conclusion is positive regulator broad activity spectrum maintenance, accelerated achieved enhanced DKK1 attenuated signaling.