Pfeilschifter J, Seyedin S M, Mundy G R
Department of Medicine/Endocrinology, University of Texas Health Science Center, San Antonio 78284.
J Clin Invest. 1988 Aug;82(2):680-5. doi: 10.1172/JCI113647.
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.
转化生长因子β1（TGF-β1）是一种在骨基质中含量丰富的多肽，由骨细胞产生，并在体外调节成骨细胞的增殖和分化功能。转化生长因子β2（TGF-β2）是一种密切相关的多肽，最初从骨基质中分离出来。先前已证明，TGF-β1可刺激新生小鼠颅骨培养物中前列腺素的产生，从而导致这些骨骼吸收。我们发现TGF-β2也有类似作用。相比之下，在长达3天的孵育期内，TGF-β1和TGF-β2在浓度比能够诱导颅骨吸收的浓度高50至100倍的情况下，未能刺激胎鼠长骨培养物中的骨吸收。用TGF-β1再孵育3天可使骨吸收降低达30%。此外，在6天孵育期的后半段，骨吸收剂白细胞介素1（IL-1）和1,25-二羟基维生素D3诱导的骨吸收被TGF-β1和TGF-β2部分或完全抑制。用羟基脲抑制DNA合成以类似TGF-β1的方式抑制长骨中的骨吸收。因此，TGF-β1和TGF-β2对长骨培养物中骨吸收的抑制作用可能是由于抑制破骨细胞前体的增殖。
