Dual modulation of osteoclast differentiation by lipopolysaccharide
Dual modulation of osteoclast differentiation by lipopolysaccharide
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DOI：
10.1359/jbmr.2002.17.7.1211
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发表时间：
2002-07-01
影响因子：
6.2
通讯作者：
Bar-Shavit, Z
中科院分区：
文献类型：
--
作者：
Zou, W;Bar-Shavit, Z
脂多糖(LPS)通过促进破骨细胞生成来调节骨吸收。在成骨细胞中，它增加RANKL、白介素1、前列腺素E-2(PGE(2))和肿瘤坏死因子-α的产生，每一种都能诱导破骨细胞的活性、活性和分化。我们研究了内毒素与破骨细胞前体的直接相互作用在促进破骨细胞前体分化中的作用。为此，我们在没有成骨细胞或基质细胞的情况下使用了骨髓单个核细胞制剂。我们发现，内毒素不能诱导这些细胞向破骨细胞分化。此外，内毒素可阻断RANKL的破骨细胞活性。然而，即使在没有外源RANKL的情况下，内毒素也是RANKL处理细胞中有效的破骨细胞诱导剂。骨保护素(OPG)不影响内毒素调节破骨细胞生成的刺激期，排除内源性RANKL的参与。无论是否经RANKL处理，脂多糖均可诱导破骨细胞前体细胞表达肿瘤坏死因子-α和白介素1β。这两种细胞因子诱导RANKL处理细胞向破骨细胞分化。为了检验这些细胞因子是否以自分泌机制介导了内毒素的作用，我们测量了它们中和对内毒素破骨细胞活性的影响。尽管中和IL-1β不影响内毒素活性，但当中和肿瘤坏死因子-α时，可观察到明显的抑制作用。然而，在内毒素抑制RANKL破骨细胞生成活性的条件下，肿瘤坏死因子-α的表达也增加。我们发现，内毒素可降低RANK和巨噬细胞集落刺激因子(M-CSF)受体的表达。综上所述，内毒素还通过与前体细胞的相互作用影响破骨细胞的形成。脂多糖通过降低RANKL受体和M-CSF受体的表达抑制RANKL活性，并通过肿瘤坏死因子-α刺激RANKL处理细胞的破骨细胞生成。
Lipopolysaccharide (LPS) modulates bone resorption by augmentation of osteoclastogenesis. It increases in osteoblasts the production of RANKL, interleukin (IL)-1, prostaglandin E-2 (PGE(2)), and TNF-alpha, each known to induce osteoclast activity, viability, and differentiation. We examined the role of direct interactions of LPS with osteoclast precursors in promoting their differentiation. To this end, we have used bone marrow mononuclear cell preparations in the absence of osteoblasts or stromal cells. We found that LPS does not induce osteoclast differentiation in these cells. Moreover, the inclusion of LPS blocked the osteoclastogenic activity of RANKL. However, LPS is a potent inducer of osteoclastogenesis in RANKL-pretreated cells, even if present in the absence of exogenous RANKL. Osteoprotegerin (OPG) does not affect the stimulatory phase of LPS modulation of osteoclastogenesis, ruling out involvement of endogenous RANKL. LPS induces the expression of TNF-alpha and IL-1beta in osteoclast precursors, regardless if they were or were not pretreated with RANKL. These two cytokines induced osteoclast differentiation in RANKL-pretreated cells. To examine if these cytokines mediate LPS effect in an autocrine mechanism, we measured the effect of their neutralization on LPS osteoclastogenic activity. Although neutralization of IL-1beta did not affect LPS activity, a marked inhibition was observed when TNF-alpha was neutralized. However, TNF-alpha expression was increased also in conditions in which LPS inhibited RANKL osteoclastogenic activity. We found that LPS reduces the expression of RANK and macrophage colony-stimulating factor (M-CSF) receptor. In summary, LPS impacts on osteoclastogenesis also via its interactions with the precursor cells. LPS inhibits RANKL activity by reducing the expression of RANK and M-CSF receptor and stimulates osteoclastogenesis in RANKL-pretreated cells via TNF-alpha.