Fuller K, Owens J M, Chambers T J
Department of Histopathology, St. George's Hospital Medical School, London, United Kingdom.
J Immunol. 1995 Jun 1;154(11):6065-72.
Cells of the osteoblastic lineage play a major role in the regulation of osteoclastic bone resorption. Recent studies have demonstrated production of chemokines by osteoblastic cells. Although these phagocyte-stimulating and proinflammatory cytokines act as chemoattractants and activators for other members of the hemopoietic lineage, their actions on osteoclasts have not been characterized. We found that macrophage inflammatory protein-1 alpha (MIP-1 alpha) and IL-8 inhibited bone resorption by rat osteoclasts, primarily through reduction in the proportion of osteoclasts resorbing bone, a pattern of inhibition previously observed in response to macrophage CSF (M-CSF). MIP-2, RANTES, MIP-1 beta, and monocyte chemotactic protein-1 were without effect on resorption. MIP-1 alpha and IL-8, but not the other chemokines, also stimulated osteoclastic motility and increased the osteoclast spread area in a dose-dependent manner, over the same concentration range as that which inhibited bone resorption. In addition, MIP-1 alpha induced osteoclast orientation in a gradient of the chemokine, and stimulated osteoclast migration. We detected no effect of chemokines on osteoclast formation or survival. Our data suggest that chemokines can promote osteoclast orientation and migration, processes that might be involved in chemotaxis; it seems appropriate that resorptive functions should be suppressed during migration. Because chemokines are proinflammatory, their actions on osteoclasts might represent mechanisms by which bone resorption is modulated by the inflammatory process when this occurs in bone. However, given that chemokines are increasingly recognized to be multifunctional and that they are produced by cells of the osteoblastic lineage, they may also be components of the physiologic regulation of bone resorption.
成骨细胞系细胞在破骨细胞性骨吸收的调节中起主要作用。最近的研究表明成骨细胞能产生趋化因子。尽管这些刺激吞噬细胞和促炎细胞因子可作为造血细胞系其他成员的趋化剂和激活剂，但其对破骨细胞的作用尚未明确。我们发现巨噬细胞炎性蛋白-1α（MIP-1α）和白细胞介素-8（IL-8）主要通过减少正在进行骨吸收的破骨细胞比例来抑制大鼠破骨细胞的骨吸收，这种抑制模式与之前观察到的巨噬细胞集落刺激因子（M-CSF）的作用相似。巨噬细胞炎性蛋白-2（MIP-2）、调节激活正常T细胞表达和分泌因子（RANTES）、MIP-1β和单核细胞趋化蛋白-1对骨吸收无影响。在抑制骨吸收的相同浓度范围内，MIP-1α和IL-8而非其他趋化因子还能刺激破骨细胞的运动性，并以剂量依赖方式增加破骨细胞的铺展面积。此外，MIP-1α可诱导破骨细胞在趋化因子梯度中定向，并刺激破骨细胞迁移。我们未检测到趋化因子对破骨细胞形成或存活的影响。我们的数据表明趋化因子可促进破骨细胞的定向和迁移，这些过程可能与趋化作用有关；在迁移过程中抑制吸收功能似乎是合适的。由于趋化因子具有促炎作用，它们对破骨细胞的作用可能代表了炎症过程发生在骨组织时调节骨吸收的机制。然而，鉴于趋化因子越来越被认为具有多种功能，且它们由成骨细胞系细胞产生，它们也可能是骨吸收生理调节的组成部分。
