Study on osteoclast activiting factor expressed by osteoblasts/stromal cells

我们研究了破骨细胞活化因子在成骨细胞/基质细胞中的表达特点。本研究建立了大量纯化单核和多核破骨细胞的方法。利用纯化方法，我们分析了成骨细胞/基质细胞激活破骨细胞的机制。(1)成骨细胞增强纯化的单核和多核破骨细胞的存活，从而导致多核破骨细胞的形成。成骨细胞还通过细胞间接触的机制刺激破骨细胞的再吸收陷窝形成活性。(2)由成骨细胞产生的M-CSF也刺激破骨细胞的存活，但不能刺激破骨细胞的陷窝形成活性。(3)从M-CSF缺陷的op/op小鼠获得的成骨细胞不仅刺激破骨细胞的存活，而且刺激它们的成孔活性。(4)成骨细胞诱导的破骨细胞小窝形成活性可被骨保护素（osteoprotegerin，ADEC）所抑制 关于我们 ODF的Oy受体）。(5)破骨细胞表达高水平的IL-1 1型受体和ODF受体（RANK）。用IL-1或ODF处理破骨细胞诱导NF-κ B活化。(6)IL-1和ODF刺激破骨细胞的陷窝形成活性。IL-1受体拮抗剂能抑制IL-1诱导的破骨细胞活化，而OPG不能抑制ODF诱导的破骨细胞活化，OPG特异性地抑制ODF诱导的破骨细胞活化。这些结果表明，成骨细胞/基质细胞表达的破骨细胞活化因子确实是ODF，其cDNA于1998年克隆。最近，研究表明TRAF6基因敲除小鼠发生了严重的骨硬化症。在TRAF6基因敲除小鼠中，在骨骼中发现了许多破骨细胞，但它们未能形成皱褶边界。由于IL-1受体和RANK与TRAF6相互作用，TRAF6介导的信号似乎对IL-1和RANK诱导的破骨细胞活化很重要。也表明NF-κ B的活化对于诱导破骨细胞的陷窝形成活性是重要的。少

We have investigated characteristics of osteoclast activating factor expressed by osteoblasts/stromal cells. The method for obtaining a large number of purified mononuclear and multinucleated osteoclasts was established in this study. Using the purification method, we analyzed the mechanism of activation of osteoclasts by osteoblasts/stromal cells.(1) Osteoblasts enhanced survival of purified mononuclear and multinucleated osteoclasts, which resulted in formation of multinucleated osteoclasts. Osteoblasts also stimulated resorption pit-forming activity of osteoclasts through a mechanism involving cell-to-cell contact.(2) M-CSF produced by osteoblasts also stimulated the survival of osteoclasts, but failed to stimulated pit-forming activity of osteoclasts.(3) Osteoblasts obtained from M-CSF-deficient op/op mice stimulated not only survival of osteoclasts but also their pit-forming activity.(4) Osteoblast-induced pit forming activity of osteoclasts was inhibited by osteoprotegerin (a dec … More oy receptor for ODF) simultaneously added.(5) Osteoclasts expressed high levels of IL-1 type 1 receptors and ODF receptors (RANK). Treatment of osteoclasts with IL-1 or ODF induced activation of NF-κB.(6) IL-1 and ODF stimulated pit-forming activity of osteoclasts. IL-1 -induced osteoclast activation was inhibited by IL-1 receptor antagonist but not OPG, whereas ODF-induced osteoclast activation was specifically inhibited by OPG.These results indicate that osteoclast activating factor expressed by osteoblasts/stromal cells is indeed ODF, the cDNA of which cloned in 1998. Recently, it was shown that TRAF6 knockout mice developed severe osteopetrosis. In TRAF6 knockout mice, many osteoclasts were found in bone but they failed to develop ruffled borders. As IL-1 receptors and RANK are shown to be interact with TRAF6, TRAF6-mediated signals appear to be important for IL-1 and RANK-induced activation of osteoclasts. It is also suggested that activation of NF-KB is important for induction of pit-forming activity of osteoclasts. Less