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Updated: Nov 16, 2025
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
DEC1 deficiency results in accelerated osteopenia through enhanced DKK1 activity and attenuated PI3KCA/Akt/GSK3β
Shuangcheng He1, Yu Guan1, Yichen Wu1
1Department of Pharmacology, Nanjing Medical University, China.
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 bone development, osteopenia and osteoporosis.
Methods And Results:
DEC1 knockout (KO) and the age-matched wild-type (WT) mice were tested for the impact of DEC1 deficiency on bone development and osteopenia as a function of age. DEC1 deficiency exhibited retarded bone development at the age of 4 weeks and osteopenic phenotype in both 4- and 24-week old mice. However, the osteopenia was more severe in the 24-week age groups. Mechanistically, DEC1 deficiency downregulated the expression of bone-enhancing genes such as Runx2 and β-catenin accompanied by upregulating DKK1, an inhibitor of the Wnt/β-catenin signaling pathway. Consistently, DEC1 deficiency favored the attenuation of the integrated PI3KCA/Akt/GSK3β signaling, a pathway targeting β-catenin for degradation. Likewise, the attenuation was greater in the 24-week age group. These changes, however, were reversed by in vivo treatment with lithium chloride, a stabilizer of β-catenin, and confirmed by gain-of-function study with DEC1 transfection into DEC1 KO bone marrow mesenchymal stem cells and loss-of-function study with siDEC1 lentiviral infection into the corresponding WT cells.
Conclusion:
DEC1 is a positive regulator with a broad activity spectrum in both bone development and maintenance, and the osteopenic phenotype accelerated by DEC1 deficiency is achieved by enhanced DKK1 activity and attenuated PI3KCA/Akt/GSK3β signaling.
Insights
Differentiated embryonic chondrocyte expressed gene 1 (DEC1) promotes bone development and maintenance. DEC1 deficiency accelerates osteopenia by downregulating bone-enhancing genes and Wnt/β-catenin signaling.
Area of Science:
- Bone Biology and Regenerative Medicine
- Molecular and Cellular Biology
- Genetics and Genomics
Background:
- Differentiated embryonic chondrocyte expressed gene 1 (DEC1) is recognized for its role in promoting osteogenesis.
- DEC1's function is crucial for counteracting bone disorders like osteopenia and osteoporosis.
Purpose of the Study:
- To investigate the impact of DEC1 deficiency on bone development and osteopenia.
- To elucidate the molecular mechanisms underlying DEC1's role in bone homeostasis.
Main Methods:
- Comparative analysis of DEC1 knockout (KO) and wild-type (WT) mice at different ages.
- Assessment of bone development and osteopenic phenotypes.
- Molecular analysis of key bone-related gene expression and signaling pathways (Runx2, β-catenin, DKK1, PI3KCA/Akt/GSK3β).
- In vivo rescue experiments using lithium chloride and gain/loss-of-function studies with DEC1 manipulation in stem cells.
Main Results:
- DEC1 deficiency led to retarded bone development and an osteopenic phenotype, which worsened with age.
- Molecularly, DEC1 deficiency downregulated osteogenic genes (Runx2, β-catenin) and upregulated the Wnt inhibitor DKK1.
- The PI3KCA/Akt/GSK3β signaling pathway, crucial for β-catenin stabilization, was attenuated in DEC1-deficient mice.
- Lithium chloride treatment and DEC1 gain/loss-of-function studies confirmed the regulatory role of DEC1 in bone homeostasis.
Conclusions:
- DEC1 acts as a positive regulator of bone development and maintenance.
- DEC1 deficiency exacerbates osteopenia through increased DKK1 activity and attenuated PI3KCA/Akt/GSK3β signaling, impacting β-catenin levels.
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