Marks S C, Iizuka T, MacKay C A, Mason-Savas A, Cielinski M J
Department of Cell Biology, University of Massachusetts Medical School, Worcester 01655-0106, USA.
Tissue Cell. 1997 Oct;29(5):589-95. doi: 10.1016/s0040-8166(97)80059-6.
The role of colony-stimulating factor-1 (CSF-1 or M-CSF) in osteoclast development is illustrated by observations that administration of exogenous CSF-1 increases osteoclast number and improves the skeletal sclerosis of two osteopetrotic mutations, toothless (tl) in the rat and osteopetrotic (op) in the mouse. We examined the effects of CSF-1 treatment on the number and ultrastructure of osteoclasts in the tibial metaphysis of normal and mutant animals of both stocks to understand the similarities and differences between these two mutations. Osteoclasts from normal animals of both stocks were abundant and possessed the ultrastructural features of active cells. These included apical areas in contact with mineralized surfaces with tightly apposed clear zones, extensive ruffled borders, and a vacuolated cytoplasm with numerous mitochondria. In toothless rats osteoclasts were difficult to locate and those present had poorly defined ruffled borders, fewer cytoplasmic vacuoles, and a basal membrane with both smooth and ruffled areas. Large lipid accumulations were often found near tl osteoclasts. Osteoclasts in op mice were difficult to find, but more numerous than in tl rats. Unlike tl osteoclasts, those of op mice possessed very well developed ruffled borders, small clear zones, and large electron-dense cytoplasmic inclusions. These cells also had unusual basal membranes with both smooth and ruffled regions. CSF-1 treatment increased the number of osteoclasts in both mutant stocks, normalizing the numbers in op mice, but not tl rats. CSF-1 injections caused dramatic changes in the morphology of tl osteoclasts, including increased incidence and size of ruffled borders and cytoplasmic vacuolization. The growth factor had little effect on ruffled borders or clear zones in op mice. Interestingly, mutant osteoclasts of both stocks exhibited a ruffled basal membrane in response to CSF-1 treatment. This increase in membrane ruffling may reflect the ability of CSF-1 to promote rapid formation of osteoclasts from mononuclear precursors in a more permissive microenvironment. Our data indicate that CSF-1 is not required for the development of at least some osteoclasts. The differences in response to CSF-1 treatment which we report lead us to speculate that additional factors may be involved in osteoclastogenesis.
集落刺激因子-1（CSF-1或M-CSF）在破骨细胞发育中的作用可通过以下观察结果得以说明：给予外源性CSF-1可增加破骨细胞数量，并改善两种骨石化突变体的骨骼硬化，即大鼠的无牙（tl）突变体和小鼠的骨石化（op）突变体。我们研究了CSF-1处理对两种品系正常和突变动物胫骨干骺端破骨细胞数量和超微结构的影响，以了解这两种突变之间的异同。两种品系正常动物的破骨细胞数量丰富，并具有活跃细胞的超微结构特征。这些特征包括与矿化表面接触的顶端区域，紧密相邻的透明区，广泛的褶皱缘，以及含有大量线粒体的空泡化细胞质。在无牙大鼠中，破骨细胞很难定位，而且存在的破骨细胞褶皱缘不清晰，细胞质空泡较少，基底膜既有光滑区域也有褶皱区域。在无牙大鼠破骨细胞附近经常发现大量脂质聚集。骨石化小鼠中的破骨细胞很难找到，但比无牙大鼠中的破骨细胞数量更多。与无牙大鼠的破骨细胞不同，骨石化小鼠的破骨细胞具有非常发达的褶皱缘、小透明区和大的电子致密细胞质内含物。这些细胞的基底膜也有不寻常的光滑和褶皱区域。CSF-1处理增加了两种突变品系中的破骨细胞数量，使骨石化小鼠中的破骨细胞数量恢复正常，但对无牙大鼠无效。CSF-1注射导致无牙大鼠破骨细胞形态发生显著变化，包括褶皱缘的发生率和大小增加以及细胞质空泡化。生长因子对骨石化小鼠的褶皱缘或透明区影响很小。有趣的是，两种品系的突变破骨细胞在CSF-1处理后均表现出基底膜褶皱。这种膜褶皱的增加可能反映了CSF-1在更宽松的微环境中促进单核前体快速形成破骨细胞的能力。我们的数据表明，至少某些破骨细胞的发育不需要CSF-1。我们报告的对CSF-1处理反应的差异使我们推测，可能有其他因素参与破骨细胞生成。
