PLXNA2 identified as a candidate gene by genome-wide association analysis for mandibular prognathism in human chondrocytes

: In a previous genome-wide association study, plexin A2 (PLXNA2) was suggested as one of the candidate genes for mandibular prognathism. PLXNA2 encodes plexin A2, a member of the plexin-A family of semaphorin co-receptors. Semaphorin 3A (sema3A) exerts an osteoprotective effect. However, to the best of our knowledge, there have been no previous studies examining the role of sema3A or plexin A2 on human chondrocytes. The objectives of the present study were to examine the function of sema3A and its receptor, plexin A2, in human chondrocytes. Normal human chondrocytes were cultured in media with either a high (100 ng/ml) or a low (1 ng/ml) concentration of sema3A, or without sema3A as a control. Cells and extracellular matrices were assayed for concentrations of protein and parathyroid hormone-related peptide receptor 1 (PTH-R1) using a bicinchoninic acid assay and an enzyme immunoassay, respectively. At culture day 7, the high and low concentrations of exogenous sema3A significantly increased the protein content compared with the control (P=0.0008 and 0.00002, respectively). At culture day 14, a high concentration of exogenous sema3A significantly increased the protein content and decreased the concentration of PTH-R1 compared with the control (P=0.002). The present study revealed novel results that exogenous sema3A suppresses the expression of PTH-R1 in human proliferative chondrocytes and suggested that sema3A may affect human chondrocytes via its receptor, plexin A2.