Cecchini M G, Hofstetter W, Halasy J, Wetterwald A, Felix R
Department of Pathophysiology, University of Berne, Switzerland.
Mol Reprod Dev. 1997 Jan;46(1):75-83; discussion 83-4. doi: 10.1002/(SICI)1098-2795(199701)46:1<75::AID-MRD12>3.0.CO;2-2.
There is a close interaction between the processes involved in osteogenesis and hemopoiesis. In developing bone, the osteoclasts, cells of hemopoietic origin, resorb and invade the calcified cartilage rudiment. As a result, the primitive marrow cavity is formed and hemopoiesis initiates. Osteogenic cells-osteoblasts and osteocytes-control the development and activity of the osteoclasts through the local release of factors. One factor responsible for this osteoblast-osteoclast interaction is colony-stimulating factor-1 (CSF-1). Studies performed on the osteopetrotic op/op mouse mutant have established that this factor is essential for proliferation and differentiation of the osteoclasts. Expression of CSF-1 receptors by mature osteoclasts and osteoclast precursors strongly suggests that CSF-1 action is exerted directly on cells of this lineage. In vivo, CSF-1 synthesis by osteoblasts is temporally and spatially related to sites of osteoclast development. Thus CSF-1 may represent one of the factors responsible for coupling hemopoiesis to osteogenesis. In vitro, osteoblasts express at least 4 transcripts encoding either a secreted or a membrane-bound form of CSF-1. At the protein level, osteoblasts in vitro synthesize the membrane-bound form and secrete the majority of CSF-1 as a proteoglycan, a small fraction of which is integrated into the matrix. These different molecular forms may locally restrict the biological action of this cytokine. Indeed, injection of recombinant human CSF-1 in op/ op mutants does not correct the osteoclast deficiency in the metaphyseal spongiosa of long bones, and sclerosis persists at this site. Similarly, the deficiency of some tissue macrophage populations in op/op mice is only partially or not at all corrected by injection of CSF-1. The expression of CSF-1 receptors by mature osteoclasts may imply that CSF-1 also influences their bone resorbing activity. Indeed, CSF-1 has been shown to induce osteoclast fusion, spreading, and survival. These findings suggest that CSF-1 is essential for the proliferation, differentiation, activity, and survival of tissue macrophages and osteoclasts, cells involved in tissue turnover. Furthermore, they corroborate the view that both osteoclasts and tissue macrophages stem from a CSF-1-dependent common precursor along the macrophage lineage.
骨生成和造血过程之间存在密切的相互作用。在发育中的骨骼中，破骨细胞是造血起源的细胞，它们吸收并侵入钙化的软骨雏形。结果，原始骨髓腔形成，造血过程启动。成骨细胞和成骨细胞通过局部释放因子来控制破骨细胞的发育和活性。负责这种成骨细胞 - 破骨细胞相互作用的一个因子是集落刺激因子 -1（CSF-1）。对骨石化op/op小鼠突变体进行的研究表明，该因子对于破骨细胞的增殖和分化至关重要。成熟破骨细胞和破骨细胞前体表达CSF-1受体，这强烈表明CSF-1的作用直接作用于该谱系的细胞。在体内，成骨细胞合成的CSF-1在时间和空间上与破骨细胞发育部位相关。因此，CSF-1可能是负责将造血与骨生成联系起来的因子之一。在体外，成骨细胞表达至少4种转录本，编码分泌型或膜结合型CSF-1。在蛋白质水平上，体外培养的成骨细胞合成膜结合型CSF-1，并将大部分CSF-1作为蛋白聚糖分泌，其中一小部分整合到基质中。这些不同的分子形式可能在局部限制了这种细胞因子的生物学作用。事实上，向op/op突变体注射重组人CSF-1并不能纠正长骨干骺端松质骨中的破骨细胞缺陷，该部位的硬化仍然存在。同样，op/op小鼠中一些组织巨噬细胞群体的缺陷通过注射CSF-1只能部分或根本无法得到纠正。成熟破骨细胞表达CSF-1受体可能意味着CSF-1也影响它们的骨吸收活性。事实上，CSF-1已被证明可诱导破骨细胞融合、铺展和存活。这些发现表明，CSF-1对于组织巨噬细胞和破骨细胞（参与组织更新的细胞）的增殖、分化、活性和存活至关重要。此外，它们证实了破骨细胞和组织巨噬细胞都起源于沿巨噬细胞谱系的CSF-1依赖性共同前体的观点。
