Fuller K, Wong B, Fox S, Choi Y, Chambers T J
St. George's Hospital Medical School, London, United Kingdom.
J Exp Med. 1998 Sep 7;188(5):997-1001. doi: 10.1084/jem.188.5.997.
TRANCE (tumor necrosis factor-related activation-induced cytokine) is a recently described member of the tumor necrosis factor superfamily that stimulates dendritic cell survival and has also been found to induce osteoclastic differentiation from hemopoietic precursors. However, its effects on mature osteoclasts have not been defined. It has long been recognized that stimulation of osteoclasts by agents such as parathyroid hormone (PTH) occurs through a hormonal interaction with osteoblastic cells, which are thereby induced to activate osteoclasts. To determine whether TRANCE accounts for this activity, we tested its effects on mature osteoclasts. TRANCE rapidly induced a dramatic change in osteoclast motility and spreading and inhibited apoptosis. In populations of osteoclasts that were unresponsive to PTH, TRANCE caused activation of bone resorption equivalent to that induced by PTH in the presence of osteoblastic cells. Moreover, osteoblast-mediated stimulation of bone resorption was abrogated by soluble TRANCE receptor and by the soluble decoy receptor osteoprotegerin (OPG), and stimulation of isolated osteoclasts by TRANCE was neutralized by OPG. Thus, TRANCE expression by osteoblasts appears to be both necessary and sufficient for hormone-mediated activation of mature osteoclasts, and TRANCE-R is likely to be a receptor for signal transduction for activation of the osteoclast and its survival.
TRANCE（肿瘤坏死因子相关激活诱导细胞因子）是肿瘤坏死因子超家族中最近发现的一个成员，它能刺激树突状细胞存活，还被发现可诱导造血前体细胞分化为破骨细胞。然而，其对成熟破骨细胞的作用尚未明确。长期以来人们认识到，甲状旁腺激素（PTH）等物质对破骨细胞的刺激是通过与成骨细胞的激素相互作用实现的，从而诱导成骨细胞激活破骨细胞。为了确定TRANCE是否介导了这种活性，我们测试了它对成熟破骨细胞的作用。TRANCE迅速引起破骨细胞运动性和铺展的显著变化，并抑制细胞凋亡。在对PTH无反应的破骨细胞群体中，TRANCE引起的骨吸收激活程度与在有成骨细胞存在时PTH诱导的程度相当。此外，可溶性TRANCE受体和可溶性诱饵受体骨保护素（OPG）可消除成骨细胞介导的骨吸收刺激，OPG可中和TRANCE对分离破骨细胞的刺激。因此，成骨细胞表达TRANCE似乎对于激素介导的成熟破骨细胞激活既是必要的也是充分的，TRANCE-R可能是破骨细胞激活及其存活信号转导的受体。
