Takahashi N, Mundy G R, Roodman G D
J Immunol. 1986 Dec 1;137(11):3544-9.
Interferon-gamma (IFN-gamma) inhibits osteoclastic bone resorption in vitro, but the mechanism responsible for this inhibition is unknown. We have used a long-term human marrow culture system that forms multinucleated cells (MNC) with osteoclast characteristics to test the effect of recombinant human IFN-gamma on MNC formation. The addition of 1,25-dihydroxy-vitamin D3 (1,25D3) at 10(-8) M to these cultures significantly increased both MNC formation and the number of nuclei per MNC. IFN-gamma at 100 U/ml strongly inhibited both of these effects of 1,25D3 in this system. IFN-gamma significantly inhibited MNC formation at very low concentrations (4 U/ml), with 10 U/ml inhibiting 1,25D3-stimulated MNC formation by 50%. In contrast, 100 U/ml of IFN-gamma were required to inhibit the growth of granulocyte-macrophage colony-forming cells, the probable progenitor for MNC, by 50%. Treatment of cultures with IFN-gamma for only the first or last week of culture significantly inhibited MNC formation stimulated by 1,25D3. Autoradiographic studies with [3H]thymidine showed that IFN-gamma did not inhibit proliferation of precursors for MNC. Additionally, IFN-gamma inhibited MNC formation stimulated by parathyroid hormone or interleukin 1. These results suggest that IFN-gamma inhibits MNC formation, and that IFN-gamma inhibits bone resorption in part by inhibiting osteoclast formation.
γ干扰素（IFN-γ）在体外可抑制破骨细胞的骨吸收，但这种抑制作用的机制尚不清楚。我们使用了一种长期的人骨髓培养系统，该系统可形成具有破骨细胞特征的多核细胞（MNC），以测试重组人IFN-γ对MNC形成的影响。向这些培养物中添加10^(-8) M的1,25-二羟基维生素D3（1,25D3）可显著增加MNC的形成以及每个MNC的细胞核数量。在该系统中，100 U/ml的IFN-γ强烈抑制了1,25D3的这两种作用。IFN-γ在非常低的浓度（4 U/ml）时就能显著抑制MNC的形成，10 U/ml的IFN-γ可抑制1,25D3刺激的MNC形成达50%。相比之下，需要100 U/ml的IFN-γ才能将粒细胞-巨噬细胞集落形成细胞（MNC可能的祖细胞）的生长抑制50%。仅在培养的第一周或最后一周用IFN-γ处理培养物，可显著抑制1,25D3刺激的MNC形成。用[3H]胸腺嘧啶进行的放射自显影研究表明，IFN-γ不会抑制MNC前体细胞的增殖。此外，IFN-γ还抑制甲状旁腺激素或白细胞介素1刺激的MNC形成。这些结果表明，IFN-γ抑制MNC的形成，并且IFN-γ部分通过抑制破骨细胞的形成来抑制骨吸收。
