Laboratory of Molecular Signaling and Stem Cells Therapy, Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, 100050, Beijing, China.
Department of Endodontics, Capital Medical University School of Stomatology, Beijing, 100050, China.
Cell Tissue Res. 2022 Aug;389(2):187-199. doi: 10.1007/s00441-022-03628-7. Epub 2022 May 11.
Tooth loss and maxillofacial bone defect are common diseases, which seriously affect people's health. Effective tooth and maxillofacial bone tissue regeneration is a key problem that need to be solved. In the present study, we investigate the role of PRMT6 in osteo/odontogenic differentiation and migration capacity by using SCAPs. Our results showed that knockdown of PRMT6 promoted the osteo/odontogenic differentiation compared with the control group, as detected by alkaline phosphatase activity, alizarin red staining, and the indicators of osteo/odontogenic differentiation measured by Western blot. In addition, overexpression of PRMT6 inhibited the osteo/odontogenic differentiation potentials of SCAPs. Then, knockdown of PRMT6 promoted the migration ability and overexpression of PRMT6 inhibited the migration ability in SCAPs. Mechanically, we discovered that the depletion of PRMT6 promoted the expression of CXCL12 by decreasing H3R2 methylation in the promoter region of CXCL12. In addition, PRMT6 formed a protein complex with LMNA, a nuclear structural protein. Depletion of LMNA inhibited the osteo/odontogenic differentiation and CXCL12 expression and increased the intranucleus PRMT6 in SCAPs. To sum up, PRMT6 might inhibit the osteo/odontogenic differentiation and migration ability of SCAPs via inhibiting CXCL12. And LMNA might be a negative regulator of PRMT6. It is suggested that PRMT6 may be a key target for SCAP-mediated bone and tooth tissue regeneration.
牙齿缺失和颌面部骨缺损是常见疾病，严重影响人们的健康。有效的牙齿和颌面部骨组织再生是需要解决的关键问题。在本研究中，我们通过使用 SCAP 研究了 PRMT6 在成骨/成牙分化和迁移能力中的作用。我们的结果表明，与对照组相比，敲低 PRMT6 可促进成骨/成牙分化，碱性磷酸酶活性、茜素红染色和 Western blot 检测的成骨/成牙分化指标均有体现。此外，过表达 PRMT6 抑制了 SCAP 的成骨/成牙分化潜能。然后，敲低 PRMT6 促进了 SCAPs 的迁移能力，而过表达 PRMT6 则抑制了其迁移能力。在机制上，我们发现 PRMT6 通过降低 CXCL12 启动子区域的 H3R2 甲基化来促进 CXCL12 的表达。此外，PRMT6 与核结构蛋白 LMNA 形成蛋白复合物。LMNA 的缺失抑制了 SCAPs 中的成骨/成牙分化和 CXCL12 表达，并增加了核内 PRMT6。总之，PRMT6 可能通过抑制 CXCL12 来抑制 SCAPs 的成骨/成牙分化和迁移能力。并且 LMNA 可能是 PRMT6 的负调控因子。提示 PRMT6 可能是 SCAP 介导的骨和牙齿组织再生的关键靶点。
