Takahashi N, MacDonald B R, Hon J, Winkler M E, Derynck R, Mundy G R, Roodman G D
J Clin Invest. 1986 Oct;78(4):894-8. doi: 10.1172/JCI112677.
Transforming growth factor-alpha (TGF-alpha) is synthesized by a variety of tumor cell lines and stimulates osteoclastic bone resorption in vitro. The mechanism by which TGF-alpha increases osteoclast activity is unknown. We used a human marrow culture system that forms osteoclast-like multinucleated cells (MNCs) to determine the effects of recombinant human TGF-alpha on MNC formation. Addition of 0.01 ng/ml TGF-alpha for the 1st week followed by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] for the subsequent 2 wk significantly increased MNCs. Treatment of these cultures with TGF-alpha without later addition of 1,25(OH)2D3 did not increase MNC formation. Autoradiographic studies revealed that TGF-alpha stimulated proliferation of precursors for MNCs, and 1,25(OH)2D3 increased their rate of fusion into MNCs. Addition of murine epidermal growth factor (EGF) (0.1 ng/ml) followed by 1,25(OH)2D3 also significantly stimulated MNC formation. These data suggest that TGF-alpha and EGF may stimulate bone resorption by increasing the proliferation of osteoclast precursors, which leads to increased numbers of osteoclasts.
转化生长因子-α（TGF-α）由多种肿瘤细胞系合成，并在体外刺激破骨细胞的骨吸收。TGF-α增加破骨细胞活性的机制尚不清楚。我们使用了一种能形成破骨细胞样多核细胞（MNCs）的人骨髓培养系统，以确定重组人TGF-α对MNC形成的影响。在第1周添加0.01 ng/ml的TGF-α，随后在接下来的2周添加1,25-二羟维生素D3 [1,25(OH)2D3]，可显著增加MNCs的数量。在这些培养物中单独使用TGF-α处理，而不随后添加1,25(OH)2D3，则不会增加MNC的形成。放射自显影研究表明，TGF-α刺激MNC前体细胞的增殖，而1,25(OH)2D3增加它们融合形成MNCs的速率。添加鼠表皮生长因子（EGF）（0.1 ng/ml），随后添加1,25(OH)2D3，也能显著刺激MNC的形成。这些数据表明，TGF-α和EGF可能通过增加破骨细胞前体的增殖来刺激骨吸收，这会导致破骨细胞数量增加。
