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

Kajii,Takashi  S.; Oka,Akira; Hatta,Mitsutoki; Yamazaki,Jun; Yamashita,Junro; Iida,Junichiro

doi:10.3892/br.2018.1128

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

Authors:
- Takashi S. Kajii
- Akira Oka
- Mitsutoki Hatta
- Jun Yamazaki
- Junro Yamashita
- Junichiro Iida
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Affiliations: Section of Orthodontics, Department of Oral Growth and Development, Fukuoka Dental College, Fukuoka 814-0913, Japan, Institute of Medical Science, Tokai University, Kanagawa 259-1193, Japan, Section of Cellular and Molecular Regulation, Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka 814-0913, Japan, Section of Fixed Prosthodontics, Department of Oral Rehabilitation, Fukuoka Dental College, Fukuoka 814-0913, Japan, Department of Orthodontics, Division of Oral Functional Science, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan
Published online on: July 11, 2018 https://doi.org/10.3892/br.2018.1128
Pages: 253-258

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Abstract

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.

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