title: Compression-dependent up-regulation of ephrin-A2 in PDL fibroblasts attenuates osteogenesis.
abstract: Members of the ephrin/Eph family have recently been shown to be involved in the regulation of bone homeostasis in a murine model. The activation of the EphB4 receptor on osteoblasts by its ligand ephrin-B2 led to stimulation of osteoblastogenesis and therefore to bone formation. The activation of ephrin-A2-EphA2 signaling on osteoblasts inhibited the activation of osteoblast-specific gene expression, leading to bone resorption. Fibroblasts within the periodontal ligament periodontal ligament may be one of the first responders to orthodontic forces. Periodontal ligament fibroblasts (PDLF) are mechanoresponsive. Members of the ephrin/Eph family might link mechanical forces received by PDLF with the regulation of osteoblastogenesis on osteoblasts of the alveolar bone. To study whether ephrin-A2 is modulated upon compression, we subjected human primary PDLF to static compressive forces (30.3 g/cm(2)). Static compressive forces significantly induced the expression of ephrin-A2, while the expression of ephrin-B2 was significantly down-regulated. Moreover, osteoblasts of the alveolar bone stimulated with ephrin-A2 in vitro significantly suppressed their osteoblastogenic gene expression (RUNX2, ALPL) and decreased signs of osteoblastic differentiation, as demonstrated by a significantly reduced ALP activity. Together, these findings establish a role for this ligand/receptor system linking mechanical forces with the regulation of osteogenesis during orthodontic tooth movement.
authors: Department of Orthodontics and Dentofacial Orthopaedics, Dental School, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors: K
authors: K
authors: Diercke
authors: S
authors: S
authors: Sen
authors: A
authors: A
authors: Kohl
authors: C J
authors: CJ
authors: Lux
authors: R
authors: R
authors: Erber
mesh_terms: D000293:Adolescent; D000539:Alveolar Process / Q000166:cytology / Q000378:metabolism*; D000704:Analysis of Variance; D016723:Bone Remodeling / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D019245:Compressive Strength; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D003799:Dental Stress Analysis; D036383:Ephrin-A2 / Q000096:biosynthesis*; D036388:Ephrin-B2 / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System; D010006:Osteoblasts / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D036104:Receptor, EphA2 / Q000096:biosynthesis; D018709:Statistics, Nonparametric; D014087:Tooth Movement Techniques; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D036383:Ephrin-A2; D036388:Ephrin-B2; C493709:RUNX2 protein, human; D036104:Receptor, EphA2