Bertolini D R, Nedwin G E, Bringman T S, Smith D D, Mundy G R
Nature. 1986;319(6053):516-8. doi: 10.1038/319516a0.
When leukocytes are exposed to mitogens or antigens in vitro, they release bone-resorbing activity into the culture supernatants which can be detected by bioassay. Like many lymphocyte-monocyte products, this activity has been difficult to purify because of its low abundance in activated leukocyte cultures and the unwieldy bioassay required to detect biological activity. Partially purified preparations of this activity inhibit bone collagen synthesis in organ cultures of fetal rat calvariae. Recent data suggest that both activated lymphocytes and monocytes release factors which could contribute to this activity. Recently, monocyte-derived tumour necrosis factor alpha (TNF-alpha) and lymphocyte-derived tumour necrosis factor beta (TNF-beta) (previously called lymphotoxin), two multifunctional cytokines which have similar cytotoxic effects on neoplastic cell lines, have been purified to homogeneity and their complementary DNAs cloned and expressed in Escherichia coli. As both of these cytokines are likely to be present in activated leukocyte supernatants, we tested purified recombinant preparations for their effects on bone resorption and bone collagen synthesis in vitro, and report here that both cytokines at 10(-7) to 10(-9) M caused osteoclastic bone resorption and inhibited bone collagen synthesis. These data suggest that at least part of the bone-resorbing activity present in activated leukocyte culture supernatants may be due to these cytokines.
当白细胞在体外接触有丝分裂原或抗原时，它们会向培养上清液中释放骨吸收活性，这种活性可通过生物测定法检测到。与许多淋巴细胞 - 单核细胞产物一样，由于其在活化白细胞培养物中的丰度较低以及检测生物活性所需的繁琐生物测定法，这种活性一直难以纯化。这种活性的部分纯化制剂可抑制胎鼠颅骨器官培养中的骨胶原合成。最近的数据表明，活化的淋巴细胞和单核细胞都会释放可能促成这种活性的因子。最近，单核细胞衍生的肿瘤坏死因子α（TNF-α）和淋巴细胞衍生的肿瘤坏死因子β（TNF-β）（以前称为淋巴毒素）这两种对肿瘤细胞系具有相似细胞毒性作用的多功能细胞因子已被纯化至同质，并且它们的互补DNA已被克隆并在大肠杆菌中表达。由于这两种细胞因子可能都存在于活化白细胞的上清液中，我们测试了纯化的重组制剂对体外骨吸收和骨胶原合成的影响，并在此报告，浓度为10^(-7)至10^(-9) M的这两种细胞因子均会引起破骨细胞性骨吸收并抑制骨胶原合成。这些数据表明，活化白细胞培养上清液中存在的骨吸收活性至少部分可能归因于这些细胞因子。
