Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures.
Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures.
复制标题
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
复制
发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Mundy,GR
中科院分区：
文献类型：
--
作者：
Pfeilschifter,J;Seyedin,SM;Mundy,GR
转化生长因子-β1是一种在骨基质中含量丰富的多肽，由骨细胞产生，在体外对成骨细胞的增殖和分化功能具有调节作用。转化生长因子-β2是一种亲缘关系密切的多肽，最初从骨基质中分离出来。此前已有研究表明，转化生长因子-β1能刺激新生小鼠颅骨培养物中前列腺素的产生，从而导致这些骨骼的吸收。我们发现了与转化生长因子-β2类似的作用。相比之下，转化生长因子-β1和转化生长因子-β2在3d孵育期内不能刺激胎鼠长骨培养的骨吸收，其浓度高达能够诱导颅骨骨吸收的浓度的50-100倍。与转化生长因子-β1共同孵育3d，骨吸收减少达30%。此外，在6d潜伏期的后半段，骨吸收药物IL-1和1，25-二羟基维生素D3诱导的骨吸收可被转化生长因子-β1和转化生长因子-β2部分或完全抑制。用羟基脲抑制DNA合成可抑制长骨的骨吸收，其抑制方式与转化生长因子-β1相似。因此，转化生长因子-β1和转化生长因子-β2抑制长骨培养中骨吸收的作用可能与抑制破骨细胞前体增殖有关。
TGF-beta 1 is a polypeptide that is abundant in bone matrix, is produced by bone cells, and modulates proliferation and differentiated functions of osteoblastic cells in vitro. TGF-beta 2 is a closely related polypeptide that was originally isolated from bone matrix. TGF-beta 1 has been shown previously to stimulate prostaglandin production in cultures of neonatal mouse calvariae, which causes these bones to resorb. We found similar effects with TGF-beta 2. In comparison, TGF-beta 1 and TGF-beta 2 failed to stimulate bone resorption in fetal rat long bone cultures during a 3-d incubation period in concentrations up to 50-100 times greater than those capable of inducing bone resorption in calvariae. Incubation with TGF-beta 1 for a further 3 d decreased bone resorption up to 30%. Moreover, bone resorption induced by the bone-resorbing agents IL 1 and 1,25-dihydroxyvitamin D3 was partially or completely inhibited by TGF-beta 1 and TGF-beta 2 during the second half of the 6-d incubation period. Inhibition of DNA synthesis with hydroxyurea inhibited bone resorption in long bones in a similar pattern to that seen with TGF-beta 1. The inhibitory effects of TGF-beta 1 and TGF-beta 2 on bone resorption in long bone cultures may therefore be due to inhibition of osteoclast precursor proliferation.