TRANSFORMING GROWTH FACTOR-BETA INHIBITS FORMATION OF OSTEOCLAST-LIKE CELLS IN LONG-TERM HUMAN MARROW CULTURES
TRANSFORMING GROWTH FACTOR-BETA INHIBITS FORMATION OF OSTEOCLAST-LIKE CELLS IN LONG-TERM HUMAN MARROW CULTURES
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DOI：
10.1073/pnas.85.15.5683
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发表时间：
1988-08-01
影响因子：
11.1
通讯作者：
ROODMAN, GD
中科院分区：
文献类型：
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作者：
CHENU, C;PFEILSCHIFTER, J;ROODMAN, GD
转化生长因子。（TGF- β）是一种在骨基质中大量存在的多肽，我们利用具有破骨细胞特征的多核细胞（MNCs）形成的人骨髓培养系统，研究了TGF- β对破骨细胞形成的影响。TGF度量。在低至1 ng/ml的浓度下强烈抑制MNC的形成。TGF度量。也完全抑制了已知刺激MNC形成的促骨因子的作用。TGF- β的抑制作用。在培养的第一周，破骨细胞样细胞的形成更为明显，这与单核破骨细胞前体的增殖期相对应。目的：探讨TGF- β的抑制作用。对MNC形成的影响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）]，这可能是MNC的前体，我们测试了TGF-. β的作用。在菌落刺激因子来源存在的情况下，CFU-GM的形成。出乎意料,TGF度量。抑制MNC形成的浓度（0.1-1 ng/ml）促进了第7天CFU-GM菌落的形成。在含有TGF- β的培养物中，CFU-GM菌落形成的增加。在培养物中形成了更多的粒细胞集落，这表明TGF-. β。可能诱导CFU-GM优先向粒细胞系细胞分化。TGF- β对CFU-GM向粒细胞而非破骨细胞前体分化的影响会通过耗尽MNC的前体池来抑制MNC的形成。这些数据提示TGF- β对成骨细胞样细胞形成的抑制作用。可能是控制局部骨反应的重要机制。
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 osteclast-like cell formation by TGF-.beta. may be an important mechanism of control of local bone resportion.