Ossification of the Pposterior Longitudinal Ligament

后纵韧带骨化

• 批准号: 17209012
• 负责人: INOUE Ituro
• 金额: $ 33.03万
• 依托单位: Tokai University (2006-2007)The University of Tokyo (2005)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17209012/
• 关键词: OPLL; ectopic ossification; expression profile; association study; SNP; Microarray analysis; アソシエーション・スタディ; 靭帯骨化

To understand the molecular pathogenesis of ossification of the posterior longitudinal ligament of the spine (OPLL), an ectopic bone formation disease, we performed c_DNA microarray analysis on cultured ligament cells from the OPLL patients to understand the molecular pathogenesis of OPLL.We identified Zinc finger protein145 (PLZF) as one of up-regulated genes and tumor necrosis factor-a stimulated gene6 (TSG-6) and one of down-regulated gene during osteoblastic differentiation. We investigated the roles of PLZF in the regulation of osteoblastic differentiation of h_MSC_s and C2C12 cells.siRNA-mediated gene-silencing of PLZF resulted in a reduction of the expression of osteoblast-specific genes such as the alkaline phosphatase (ALP), collagen 1A1 (COL1A1), Runx2/cbfal (CBFA1), and osteocalcin (OCN) genes in the presence of OS in hMSCs.The overexpression of PLZF can induce CBFA1 induction suggestiong PLZF is an upstream regulator of CBFA1 and thereby might participate in promoting the ossification of spinal ligament cells in OPLL patients. Adenoirus-mediated TSG-6 overexpression in hMSCs resulted in suppression of oseoblastic differentiation induced by either BMP-2 or OS.TSG-6 can bind to BMP-2 directly, thereby could inhibit BMP-2 signaling.Taken together, these findings indicate that PLZF and TSG-6 play important roles in early osteoblastic differentiation.

为了了解脊柱后纵韧带骨化（OPLL）的分子发病机制，OPLL是一种异位骨形成疾病，为了探讨OPLL的分子发病机制，我们对OPLL患者的韧带细胞进行了c_DNA微阵列分析，确定了锌指蛋白145（PLZF）是OPLL的上调基因，肿瘤坏死因子-α刺激基因6（TSG-6）是OPLL的下调基因。成骨细胞分化过程中的调控基因。我们研究了PLZF在h_MSC_s和C2 C12细胞成骨分化调控中的作用。siRNA介导的PLZF基因沉默导致成骨细胞特异性基因如碱性磷酸酶（ALP）、胶原1A 1（COL 1A 1）、Runx 2/cbfal（CBFA 1）、骨钙素（OCN）PLZF的过表达可诱导CBFA 1的诱导表达，说明PLZF是CBFA 1的上游调控因子，可能参与促进脊髓韧带细胞的成骨OPLL患者腺病毒介导的TSG-6在hMSCs中过表达可抑制BMP-2或OS诱导的成骨细胞分化，TSG-6可直接与BMP-2结合，从而抑制BMP-2信号通路，这些结果表明PLZF和TSG-6在早期成骨细胞分化中起重要作用。

项目成果

The small heat shock protein alphaB-crystallin inhibits differentiation-induced caspase 3 activation and myogenic differentiation

小热休克蛋白 αB-晶状体蛋白抑制分化诱导的 caspase 3 激活和肌原性分化

• 发表时间: 2006
• 期刊: BiolPharm Bull 29
• 作者: Ikeda R;Yoshida K;Ushiyama M;Yamaguchi T;Iwashita K;Futagawa T;Shibayama Y;Oiso S;Takeda Y;Kariyazono H;Furukawa T;Nakamura K;Akiyama S;Inoue I;Yamada K.
• 通讯作者: Yamada K.

K-I Psthopysiological roles of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress

K-I 内皮素在机械应力引起的人脊柱韧带异位骨化中的生理作用

• 发表时间: 2006
• 期刊: Calcif Tissue Int 79
• 作者: Iwasawa T;Iwasaki K;Sawada T;Okada A;Ueyama K;Motomura S;Harata S;Inoue I;Toh S;Furukawa
• 通讯作者: Furukawa

Integration of hepatitis B virus DNA into the MPP (mixed lineage leukemia) 4 gene and rearrangements of MLL4 in human hepatocellular carcinoma cells.

乙型肝炎病毒 DNA 与 MPP（混合谱系白血病）4 基因的整合以及人肝细胞癌细胞中 MLL4 的重排。

• 期刊: Hum Mutat (In press)
• 作者: Saigo;K・Yoshida;K・Ikeda;R・Sakamoto;Y・Murakami;Y・Urashima;T・Asano;T・Kenmochi;T・Inoue;I.
• 通讯作者: I.

Ossification of the Posterior Longitudinal Ligament

• DOI: 10.1093/med/9780190887773.003.0009
• 发表时间: 2018-11
• 期刊: Spinal Neurosurgery
• 作者: T. Vogel;Hansen Deng;P. Mummaneni

COL6A1,the candidate gene for ossification of posterior longitudinal ligament,is associated with diffuse idiopathic skeletal hyperostosis in Japanese

COL6A1是后纵韧带骨化的候选基因，与日本弥漫性特发性骨骼骨质增生有关

• 发表时间: 2005
• 期刊: Spine 30
• 作者: Tsukahara S;Miyazawa N;Akagawa H;Forejtova S;Pavelka K;Tanaka T;Toh S;Tajima A;Akiyama I;Inoue I.
• 通讯作者: Inoue I.