Chenu C, Pfeilschifter J, Mundy G R, Roodman G D
Audie Murphy Veterans Administration Hospital, San Antonio, TX 78284.
Proc Natl Acad Sci U S A. 1988 Aug;85(15):5683-7. doi: 10.1073/pnas.85.15.5683.
Transforming growth factor beta (TGF-beta), a polypeptide present in abundant amounts in bone matrix, was examined for its effects on osteoclast formation by using a human bone marrow culture system in which multinucleated cells (MNCs) with osteoclast characteristics form. TGF-beta strongly inhibited MNC formation at concentrations as low as 1 ng/ml. TGF-beta also completely suppressed the effects of osteotropic factors known to stimulate MNC formation. The inhibitory effect of TGF-beta on osteoclast-like cell formation was more pronounced during the first week of culture, which corresponds to the period of proliferation of mononuclear osteoclast precursors. To examine whether the inhibitory effects of TGF-beta on MNC formation could be due to inhibition of the granulocyte/macrophage progenitor cell [colony-forming unit granulocyte/macrophage (CFU-GM)], the probable precursor for MNC, we tested the effects of TGF-beta on CFU-GM formation in presence of a source of colony-stimulating factor. Unexpectedly, TGF-beta at concentrations (0.1-1 ng/ml) that were inhibitory for MNC formation enhanced day 7 CFU-GM colony formation. This increase in CFU-GM colony formation seen in cultures containing TGF-beta resulted from significantly more granulocytic colonies being formed in the cultures, suggesting that TGF-beta may induce CFU-GM to differentiate preferentially to cells of the granulocytic lineage. Differentiation of CFU-GM to granulocytes rather than osteoclast precursors in response to TGF-beta would result in inhibition of MNC formation by depleting the precursor pool for MNC. These data suggest that inhibition of osteoclast-like cell formation by TGF-beta may be an important mechanism of control of local bone resorption.
转化生长因子β（TGF-β）是一种大量存在于骨基质中的多肽，我们利用一种人类骨髓培养系统来检测其对破骨细胞形成的影响，在该系统中会形成具有破骨细胞特征的多核细胞（MNCs）。TGF-β在低至1 ng/ml的浓度下就能强烈抑制MNC的形成。TGF-β还能完全抑制已知可刺激MNC形成的促骨因子的作用。TGF-β对破骨细胞样细胞形成的抑制作用在培养的第一周更为明显，这与单核破骨细胞前体的增殖期相对应。为了检测TGF-β对MNC形成的抑制作用是否可能是由于抑制了粒细胞/巨噬细胞祖细胞[集落形成单位粒细胞/巨噬细胞（CFU-GM）]（MNC的可能前体），我们在存在集落刺激因子来源的情况下测试了TGF-β对CFU-GM形成的影响。出乎意料的是，对MNC形成具有抑制作用的浓度（0.1 - 1 ng/ml）的TGF-β增强了第7天CFU-GM集落的形成。在含有TGF-β的培养物中观察到的CFU-GM集落形成的增加是由于培养物中形成了明显更多的粒细胞集落，这表明TGF-β可能诱导CFU-GM优先分化为粒细胞系细胞。CFU-GM对TGF-β的反应是分化为粒细胞而不是破骨细胞前体，这将通过耗尽MNC的前体池来抑制MNC的形成。这些数据表明，TGF-β对破骨细胞样细胞形成的抑制可能是控制局部骨吸收的一个重要机制。
