Endogenous Production of TGF-β Is Essential for Osteoclastogenesis Induced by a Combination of Receptor Activator of NF-κB Ligand and Macrophage-Colony- Stimulating Factor1
Endogenous Production of TGF-β Is Essential for Osteoclastogenesis Induced by a Combination of Receptor Activator of NF-κB Ligand and Macrophage-Colony- Stimulating Factor1
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TGF-β 的内源生成对于 NF-κB 配体受体激活剂和巨噬细胞集落刺激因子 1 组合诱导的破骨细胞生成至关重要
作者：
T. Kaneda;T. Nojima;M. Nakagawa;A. Ogasawara;H. Kaneko;Takuya Sato;H. Mano;M. Kumegawa;Y. Hakeda
破骨细胞是主要负责骨吸收的细胞，其分化受多种促骨激素和细胞因子控制。在这些因子中，NF-κB受体激活因子（RANK）配体（RANKL）最近被克隆为在M-CSF存在下破骨细胞生成的重要诱导剂。在此，我们从小鼠未分级骨细胞中分离出单核细胞/巨噬细胞（M/Mφ）样造血细胞的无基质群体，这些细胞能够通过可溶性RANKL（sRANKL）和M-CSF处理分化为成熟破骨细胞。然而，破骨细胞形成的效率较低，这表明需要额外的因素。分离的M/Mφ样造血细胞表达TGF-β及其I、II型受体。因此，我们研究了TGF-β对破骨细胞生成的影响。TGF-β与sRANKL和M-CSF的组合促进几乎所有M/Mφ样造血细胞向破骨细胞谱系的细胞分化。中和抗TGF-β抗体可抑制破骨细胞的生成。在未分级骨细胞培养物中也观察到这些TGF-β效应，并且抗TGF-β阻断了1，25-二羟维生素D3的刺激效应。TGF-β预处理的M/Mφ样造血细胞NF-κB核转位较未处理的细胞明显增强，但TGF-β对RANKL受体RANK的表达无明显上调作用。我们的研究结果表明，TGF-β是破骨细胞生成的一个必要的自分泌因子。
Differentiation of osteoclasts, the cells primarily responsible for bone resorption, is controlled by a variety of osteotropic hormones and cytokines. Of these factors, receptor activator of NF-κB (RANK) ligand (RANKL) has been recently cloned as an essential inducer of osteoclastogenesis in the presence of M-CSF. Here, we isolated a stroma-free population of monocyte/macrophage (M/Mφ)-like hemopoietic cells from mouse unfractionated bone cells that were capable of differentiating into mature osteoclasts by treatment with soluble RANKL (sRANKL) and M-CSF. However, the efficiency of osteoclast formation was low, suggesting the requirement for additional factors. The isolated M/Mφ-like hemopoietic cells expressed TGF-β and type I and II receptors of TGF-β. Therefore, we examined the effect of TGF-β on osteoclastogenesis. TGF-β with a combination of sRANKL and M-CSF promoted the differentiation of nearly all M/Mφ-like hemopoietic cells into cells of the osteoclast lineage. Neutralizing anti-TGF-β Ab abrogated the osteoclast generation. These TGF-β effects were also observed in cultures of unfractionated bone cells, and anti-TGF-β blocked the stimulatory effect of 1,25-dihydroxyvitamin D3. Translocation of NF-κB into nuclei induced by sRANKL in TGF-β-pretreated M/Mφ-like hemopoietic cells was greater than that in untreated cells, whereas TGF-β did not up-regulate the expression of RANK, the receptor of RANKL. Our findings suggest that TGF-β is an essential autocrine factor for osteoclastogenesis.
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转化生长因子-β1 对成骨细胞 MC3T3-E1 细胞中前列腺素 G/H 合酶-2 表达的调节。
DOI：
10.1210/endo.138.11.5495
发表时间：
1997
期刊：
Endocrinology.
影响因子：
--
作者：
Pilbeam,C;Rao,Y;Voznesensky,O;Kawaguchi,H;Alander,C;Raisz,L;Herschman,H
通讯作者：
Herschman,H
DOI：
10.1073/pnas.85.15.5683
发表时间：
1988-08-01
影响因子：
11.1
作者：
CHENU, C;PFEILSCHIFTER, J;ROODMAN, GD
通讯作者：
ROODMAN, GD
DOI：
--
发表时间：
1998-04
期刊：
The American journal of pathology
影响因子：
--
作者：
E. Gravallese;Y. Harada;Jeng-Tzang Wang;A. Gorn;T. Thornhill;S. Goldring
通讯作者：
E. Gravallese;Y. Harada;Jeng-Tzang Wang;A. Gorn;T. Thornhill;S. Goldring
影响因子：
20.3
作者：
J. Cashman;A. Eaves;E. Raines;R. Ross;C. Eaves
通讯作者：
J. Cashman;A. Eaves;E. Raines;R. Ross;C. Eaves
转化生长因子β抑制胎鼠长骨培养物中的骨吸收。
DOI：
10.1172/jci113647
发表时间：
1988
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Pfeilschifter,J;Seyedin,SM;Mundy,GR
通讯作者：
Mundy,GR