Lees R L, Heersche J N
Department of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
J Bone Miner Res. 1999 Jun;14(6):937-45. doi: 10.1359/jbmr.1999.14.6.937.
Several reports indicate that macrophage colony stimulating factor (MCSF) is one of the major factors required for osteoclast proliferation and differentiation. Paradoxically, it has also been reported that MCSF inhibits osteoclastic activity. We therefore decided to investigate in detail the effects of MCSF on resorption and osteoclast formation to try and clarify this issue. Osteoclast-containing cultures were obtained from rabbit long bones and cultured on plastic culture dishes or devitalized bovine bone slices. MCSF (4-400 ng/ml) stimulated osteoclastic bone resorption in a time-dependent manner and at all doses examined. After 48 h of culture in the presence of MCSF, we observed a 2-fold increase in the total area of bone resorbed, as well as a significant increase in the area of bone resorbed per osteoclast and the number of resorption pits per osteoclast. This effect was paralleled by an increase in the number of larger osteoclasts (as determined by the number of nuclei per cell) and an increase in the size and depth of the resorption pits. Since the total number of osteoclasts remained the same, the MCSF-induced increase in resorptive activity appeared to be related to an increase in the average size of the osteoclasts. When resorption was expressed as the amount of bone resorbed per osteoclast nucleus, larger osteoclasts resorbed more per nucleus, suggesting that large osteoclasts, as a population, are more effective resorbers than small osteoclasts. Interestingly, when osteoclasts were plated at one-fifth the standard density, the amount of bone resorbed per osteoclast decreased considerably, indicating that resorptive activity is also affected by cell density of osteoclasts and/or of other cells present. However, at this lower density MCSF still increased osteoclast size and resorption by the same fold increase over control, suggesting that the effect of MCSF was independent of factors related to cell density.
几份报告表明，巨噬细胞集落刺激因子（MCSF）是破骨细胞增殖和分化所需的主要因子之一。矛盾的是，也有报道称MCSF会抑制破骨细胞活性。因此，我们决定详细研究MCSF对骨吸收和破骨细胞形成的影响，以试图阐明这个问题。从兔长骨中获取含破骨细胞的培养物，并在塑料培养皿或失活的牛骨切片上培养。MCSF（4 - 400 ng/ml）以时间和剂量依赖性方式刺激破骨细胞骨吸收。在MCSF存在下培养48小时后，我们观察到骨吸收总面积增加了2倍，每个破骨细胞的骨吸收面积以及每个破骨细胞的吸收陷窝数量也显著增加。这种效应伴随着较大破骨细胞数量的增加（通过每个细胞的核数量确定）以及吸收陷窝的大小和深度增加。由于破骨细胞总数保持不变，MCSF诱导的吸收活性增加似乎与破骨细胞的平均大小增加有关。当将吸收表示为每个破骨细胞核吸收的骨量时，较大的破骨细胞每个核吸收更多的骨，这表明作为一个群体，大的破骨细胞比小的破骨细胞更有效地进行吸收。有趣的是，当破骨细胞以标准密度的五分之一接种时，每个破骨细胞吸收的骨量显著减少，这表明吸收活性也受破骨细胞和/或其他存在细胞的细胞密度影响。然而，在这种较低密度下，MCSF仍然使破骨细胞大小和吸收增加的倍数与对照相同，这表明MCSF的作用与细胞密度相关因素无关。
