Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, China.
Department of Implantology, School of Stomatology, Shandong University, Jinan, China.
J Cell Mol Med. 2019 Oct;23(10):6690-6699. doi: 10.1111/jcmm.14545. Epub 2019 Aug 2.
Tyrosine-protein phosphatase non-receptor type 2 (PTPN2) is an important protection factor for diabetes and periodontitis, but the underlying mechanism remains elusive. This study aimed to identify the substrate of PTPN2 in mediating beneficial effects of 25-Hydroxyvitamin D (25(OH)2D ) on diabetic periodontitis. 25(OH)2D photo-affinity probe was synthesized with the minimalist linker and its efficacy to inhibit alveolar bone loss, and inflammation was evaluated in diabetic periodontitis mice. The probe was used to pull down the lysates of primary gingival fibroblasts. We identified PTPN2 as a direct target of 25(OH)2D , which effectively inhibited inflammation and bone resorption in diabetic periodontitis mice. In addition, we found that colony-stimulating factor 1 receptor (CSF1R) rather than JAK/STAT was the substrate of PTPN2 to regulate bone resorption. PTPN2 direct interacted with CSF1R and dephosphorylated Tyr807 residue. In conclusion, PTPN2 dephosphorylates CSF1R at Y807 site and inhibits alveolar bone resorption in diabetic periodontitis mice. PTPN2 and CSF1R are potential targets for the therapy of diabetic periodontitis or other bone loss-related diseases.
酪氨酸蛋白磷酸酶非受体型 2（PTPN2）是糖尿病和牙周炎的重要保护因素，但潜在机制仍不清楚。本研究旨在确定 PTPN2 的底物在介导 25-羟维生素 D（25（OH）2D）对糖尿病牙周炎的有益作用中的作用。用最小化接头合成了 25（OH）2D 光亲和探针，并评估了其抑制糖尿病牙周炎牙槽骨丢失和炎症的功效。该探针用于下拉原代牙龈成纤维细胞的裂解物。我们确定 PTPN2 是 25（OH）2D 的直接靶标，它可有效抑制糖尿病牙周炎小鼠的炎症和骨吸收。此外，我们发现集落刺激因子 1 受体（CSF1R）而不是 JAK/STAT 是 PTPN2 调节骨吸收的底物。PTPN2 直接与 CSF1R 相互作用，并使 Tyr807 残基去磷酸化。总之，PTPN2 使 CSF1R 在 Y807 位点去磷酸化，并抑制糖尿病牙周炎小鼠的牙槽骨吸收。PTPN2 和 CSF1R 是治疗糖尿病牙周炎或其他与骨丢失相关疾病的潜在靶点。
