TR1, a new member of the tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption
TR1, a new member of the tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption
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DOI：
10.1096/fasebj.12.10.845
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发表时间：
1998-07-01
期刊：
影响因子：
4.8
通讯作者：
Ni, J
中科院分区：
文献类型：
--
作者：
Kwon, BS;Wang, SA;Ni, J
肿瘤坏死因子受体（TNFR）超家族的一个新成员显示出与破骨细胞生成抑制和成纤维细胞增殖相关的活性。这个新成员，称为TR 1，是从表达序列标签数据库的搜索中鉴定的，编码401个氨基酸，具有21个残基的信号序列。与TNFR的其他成员不同，TR 1不含跨膜结构域，并作为62 kDa糖蛋白分泌。TR 1 gem定位于染色体8 q23 -24.1，其mRNA在原代成骨细胞、成骨肉瘤细胞系和原代成纤维细胞上大量表达。在单核细胞系（THP-1）和人成纤维细胞中检测到TR 1的受体。Scatchard分析表明两类高和中高亲和力受体，kD分别约为45和320 pM。重组TRI诱导人包皮成纤维细胞的增殖，并增强TNF诱导的这些细胞的增殖。在成骨细胞和骨髓细胞的共培养系统中，重组TR 1完全抑制了破骨细胞样多核细胞形成的分化，在几种骨吸收因子的存在下。TR 1还强烈抑制成熟破骨细胞对牙本质切片的骨吸收功能，并降低胎儿长骨器官培养物中Ca-45的释放。抗TR 1单克隆抗体在小鼠骨髓培养中促进破骨细胞的形成。这些结果表明，TRI在成纤维细胞生长和破骨细胞分化及其功能中具有广泛的生物活性。Kwon，B.美国，王，S.，Udagawa，N.，Haridas，V.，李，Z. H、Rim，K. K.，哦，K。- O.，格林，J.，李，Y.，苏，J.，根茨，R.，Aggarwal，B. B.，TR 1是肿瘤坏死因子受体超家族的新成员，可诱导成纤维细胞增殖，抑制破骨细胞生成和骨吸收。
A newly identified member of the tumor necrosis factor receptor (TNFR) superfamily shows activities associated with osteoclastogenesis inhibition and fibroblast proliferation. This new member, called TR1, was identified from a search of an expressed sequence tag database, and encodes 401 amino acids with a 21-residue signal sequence. Unlike other members of TNFR, TR1 does not contain a transmembrane domain and is secreted as a 62 kDa glycoprotein. TR1 gem maps to chromosome 8q23-24.1 and its mRNA is abundantly expressed on primary osteoblasts, osteogenic sarcoma cell lines, and primary fibroblasts. The receptors for TR1 were detected on a monocytic cell line (THP-1) and in human fibroblasts. Scatchard analyses indicated two classes of high and medium-high affinity receptors with a kD of approximately 45 and 320 pM, respectively. Recombinant TRI induced proliferation of human foreskin fibroblasts and potentiated TNF-induced proliferation in these cells. In a coculture system of osteoblasts and bone marrow cells, recombinant TR1 completely inhibited the differentiation of osteoclast-like multinucleated cell formation in the presence of several bone-resorbing factors. TR1 also strongly inhibited bone-resorbing function on dentine slices by mature osteoclasts and decreased Ca-45 release in fetal long-bone organ cultures. Anti-TR1 monoclonal antibody promoted the formation of osteoclasts in mouse marrow culture assays. These results indicate that TRI has broad biological activities in fibroblast growth and in osteoclast differentiation and its functions.-Kwon, B. S., Wang, S., Udagawa, N., Haridas, V., Lee, Z. H., Rim, K. K., Oh, K.-O., Greene, J., Li, Y., Su, J., Gentz., R., Aggarwal, B. B., Ni, J. TR1, a new member of tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption.