Identifying differences in molecular characteristics relevant for remodelling of periodontal ligament stem cells from upper and lower jaw

Abstract

Background Clinical experience holds that the precise localization of periodontal defects greatly influences the velocity and effectiveness of wound healing and bone remodelling. Periodontal healing is quicker and more efficient in the maxilla (upper jaw) than in the mandible (lower jaw). Differences in blood supply, innervation, and odontogenesis of upper vs. lower jaw may all influence healing, but cell-intrinsic differences may also exist. Few studies focused on cell signaling in mechanically stimulated human periodontal ligament stem cells (PDLSC), none of which considered the differences between mandible and maxilla. Methods To unravel differences in molecular mechanisms and pathways in PDLSC using kinomics technology. Cells were characterized in terms of stem cell surface markers (CD34, CD45, CD73, CD90 and CD105), proliferation and differentiation capacity (adipogenic, osteogenic and chondrogenic). Besides, the kinase activity was analyzed via a multiplex kinase activity profiling technology. The phosphorylation status of cellular proteins in upper and lower jaw PDLSC cells from healthy donors is presented. We map differential kinase activity in known gene regulatory networks using network analysis to explain the observed cell-intrinsic differences in growth and regeneration of these cells. Results Upstream kinase analysis revealed two EphA receptors that were significantly stronger expressed in the mandible compared to maxilla. EphA4 signaling is known to inhibit osteogenic differentiation. Pathway analysis revealed that PI3K-Akt pathway is more active in the lower jaw. Conclusion Our findings showed that PDLSC from upper jaw have a significant higher proliferation rate and better differentiation capability. Results indicate differential activation of gene regulatory pathways in PDLSC from upper vs. lower jaw, which should be considered in studies regarding the regenerative capacity of PDLSC.