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SMURF1 Affects Dental Implant Integration in Diabetes By Regulating PKG2 Expression
Xue-Qin Wei1, Sheng-Zhi Zhang2
1Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. XueQinWei12@163.com.
Applied Biochemistry and Biotechnology
|July 19, 2025
Summary
In type II diabetes mellitus (T2DM), SMAD Specific E3 Ubiquitin Protein Ligase 1 (SMURF1) increases and reduces protein kinase type 2 (PKG2) via ubiquitination. This impairs dental implant bone integration.
Area of Science:
- Biomaterials Science
- Cell Biology
- Endocrinology
Background:
- Type II diabetes mellitus (T2DM) is linked to poor dental implant outcomes, impacting patient quality of life.
- Protein kinase type 2 (PKG2) plays a role in osteogenic differentiation, crucial for implant success.
Purpose of the Study:
- To investigate the role of SMAD Specific E3 Ubiquitin Protein Ligase 1 (SMURF1) in dental implant osseointegration in T2DM.
- To elucidate the mechanism by which SMURF1 affects PKG2 and osteogenic differentiation via ubiquitination.
Main Methods:
- Established T2DM rat and high-glucose-induced bone marrow mesenchymal stem cell (BMSC) models.
- Assessed osteogenic differentiation, glucose/insulin levels, and inflammation.
- Quantified levels of PKG2, SMURF1, and endoplasmic reticulum stress markers using PCR and Western blot.
- Analyzed SMURF1-PKG2 interaction and PKG2 ubiquitination via co-immunoprecipitation.
Main Results:
- T2DM rats showed insulin resistance and reduced PKG2/Runx2 expression post-implantation.
- High glucose decreased BMSC osteogenic differentiation and PKG2 levels, which were restored by proteasome inhibition.
- SMURF1, upregulated in T2DM, targets PKG2 for ubiquitination, reducing its levels and osteogenic differentiation.
- PKG2 overexpression or PKG2 activation (cinaciguat) reversed SMURF1-induced negative effects.
Conclusions:
- SMURF1-mediated ubiquitination of PKG2 is a key mechanism impairing osteogenic differentiation in T2DM.
- Targeting SMURF1 or enhancing PKG2 activity may improve dental implant osseointegration in diabetic patients.
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