PTPN2 regulates osseointegration of implants in Type 2 diabetes mellitus via CSF1 CSF1R signaling pathway

Background

Type 2 diabetes mellitus (T2DM) can result in unsatisfactory osseointegration. Many evidences indicated that Vitamin D can improve implant osseointegration of diabetes patients. PTPN2 (Protein tyrosine phosphatase non-receptor type 2) is a tyrosine-specific phosphatase and ubiquitously expressed in various cells of the human body. Recent researches demonstrated that vitamin D3 can improve osseointegration through positively regulating PTPN2, but the potential mechanism has not been elucidated.

Aim/Hypothesis

In present study we aimed to investigate the crosstalk of PTPN2 and CSF-1 CSF1R signaling in the regulation of osseointegration in the condition of diabetic periodontitis.

Materials and Methods

In this project, 25VD3 photoaffinity probes have been successfully synthesized and intended for exploring the targeted regulating relationship between VD3 VDR and PTPN2 through small molecule affinity purification technology combined with mass spectrometry technology. The probe was used to pull-down the lysates of mononuclear phagocyte system (THP-1). We identified PTPN2 as a direct target of 25(OH)2D3, which effectively protected the osseointegration of implants in type 2 diabetic mice. And the dephosphorylation effect of PTPN2 on its substrate CSF-1R will be explored by immunoprecipitation.

Results

25(OH)2D3 probe did not compromise biological activity of 25(OH)2D3, and it is suitable for target identification. 25(OH)2D3 targets PTPN2 and increases its phosphatase activity in type 2 diabetes. 25(OH)2D3 stimulates PTPN2 phosphatase activity. Colony stimulating factor 1 receptor (CSF1R) was the substrate of PTPPN2 to regulate osseointegration. PTPN2 direct interacted with CSF1R.

Conclusion and Clinical Implications

PTPN2 and CSF1R are potential targets for the therapy of poor osseointegration in type 2 diabetic periodontitis. This study can provide new theoretical basis and treatment targets for improving osseointegration and osteoclast-related diseases in T2DM.