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）这种异位骨形成疾病的分子发病机制，我们对 OPLL 患者培养的韧带细胞进行了 c_DNA 微阵列分析，以了解 OPLL 的分子发病机制。我们鉴定了锌指Protein145 (PLZF) 是成骨细胞过程中上调基因和肿瘤坏死因子-a 刺激基因 6 (TSG-6) 和下调基因之一差异化。我们研究了 PLZF 在 h_MSC_s 和 C2C12 细胞成骨细胞分化调节中的作用。siRNA 介导的 PLZF 基因沉默导致成骨细胞特异性基因的表达减少，例如碱性磷酸酶 (ALP)、胶原蛋白 1A1 ( hMSC 中 OS 存在时，COL1A1)、Runx2/cbfal (CBFA1) 和骨钙素 (OCN) 基因。 PLZF 过表达可诱导 CBFA1 诱导，提示 PLZF 是 CBFA1 的上游调节因子，因此可能参与促进 OPLL 患者脊柱韧带细胞的骨化。 hMSCs 中腺病毒介导的 TSG-6 过表达导致 BMP-2 或 OS 诱导的成骨细胞分化受到抑制。TSG-6 可以直接与 BMP-2 结合，从而抑制 BMP-2 信号传导。综上所述，这些发现表明PLZF和TSG-6在早期成骨细胞分化中发挥重要作用。

项目成果

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.

Pathopysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress

内皮素在机械应力引起的人脊柱韧带异位骨化中的病理生理作用

• 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 K-I.
• 通讯作者: Furukawa K-I.

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

Gene expression changes during the chondrogenic differentiation of human mesenchymal stem cells

• DOI: 10.3923/jbs.2007.729.736
• 发表时间: 2007-01-01
• 期刊: J. Boil. Sci
• 作者: Ikeda, R.