Division of Oral Biology and Disease Control, Department of Periodontology, Osaka University Graduate School of Dentistry, Suita, Japan.
Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
J Periodontal Res. 2018 Apr;53(2):200-209. doi: 10.1111/jre.12507. Epub 2017 Oct 24.
Single nucleotide polymorphisms (SNPs) of paraoxonase 1 (PON1) are known to be associated with the pathogenesis of osteoporosis and periodontitis. However, the effects of PON1 on the osteoblastic differentiation of periodontal ligament (PDL) cells are unclear. In this study, we examined the effects of PON1 on the osteoblastic differentiation of PDL cells, and analysed the role of PON1 SNPs on the pathogenesis of aggressive periodontitis (AgP) in the Japanese population.
Human PDL (HPDL) cells were exposed to the PON1 plasmid and PON1 inhibitor, 2-hydroxyquinoline, and cultured in mineralization medium. Expression of calcification-related genes and calcified nodule formation were assessed by real-time PCR, an alkaline phosphatase (ALPase) activity assay and Alizarin red staining. Sanger sequencing was performed to evaluate whether PON1 SNPs are associated with the pathogenesis of AgP in Japanese people.
During osteoblastic differentiation of HPDL cells, expression of PON1 mRNA increased in a time-dependent manner. PON1 stimulated an increase in expression of mRNA for calcification-related genes, as well as ALPase activity. In contrast, 2-hydroxyquinoline clearly inhibited the expression of calcification-related genes, ALPase activity and calcified nodule formation in HPDL cells. Moreover, there was a statistically significant difference in the minor allele frequency of PON1 SNP rs854560 between the Japanese control database and patients with AgP in the Japanese population (P = .0190).
PON1 induced cytodifferentiation and mineralization of HPDL cells, and PON1 SNP rs854560 may be associated with the pathogenesis of AgP in the Japanese population.
已知对氧磷酶 1(PON1)的单核苷酸多态性(SNP)与骨质疏松症和牙周炎的发病机制有关。然而,PON1 对牙周韧带(PDL)细胞成骨分化的影响尚不清楚。在本研究中,我们研究了 PON1 对 PDL 细胞成骨分化的影响,并分析了 PON1 SNP 在日本人群侵袭性牙周炎(AgP)发病机制中的作用。
将人牙周膜(HPDL)细胞暴露于 PON1 质粒和 PON1 抑制剂 2-羟基喹啉,并在矿化培养基中培养。通过实时 PCR、碱性磷酸酶(ALPase)活性测定和茜素红染色评估钙化相关基因的表达和钙化结节形成。采用 Sanger 测序评估 PON1 SNP 是否与日本人 AgP 的发病机制有关。
在 HPDL 细胞的成骨分化过程中,PON1 mRNA 的表达随时间呈时间依赖性增加。PON1 刺激钙化相关基因 mRNA 的表达增加,以及 ALPase 活性。相比之下,2-羟基喹啉明显抑制 HPDL 细胞中钙化相关基因、ALPase 活性和钙化结节形成的表达。此外,PON1 SNP rs854560 在日本对照数据库和日本人群中 AgP 患者之间的次要等位基因频率存在统计学显著差异(P =.0190)。
PON1 诱导 HPDL 细胞的细胞分化和矿化,PON1 SNP rs854560 可能与日本人群中 AgP 的发病机制有关。