Kodama H, Nose M, Niida S, Yamasaki A
Department of Anatomy, Ohu University School of Dentistry, Koriyama, Japan.
J Exp Med. 1991 May 1;173(5):1291-4. doi: 10.1084/jem.173.5.1291.
Severe deficiency of osteoclasts, monocytes, and peritoneal macrophages in osteopetrotic (op/op) mutant mice is caused by the absence of functional macrophage colony-stimulating factor (M-CSF). To clarify the role of M-CSF in the osteoclast differentiation, we established a clonal stromal cell line OP6L7 capable of supporting hemopoiesis from newborn op/op mouse calvaria. Although very few macrophages appeared in the cocultures of bone marrow cells and OP6L7 cells, a 50-fold larger number of macrophages was detected in the day 7 cocultures when purified recombinant human M-CSF (rhM-CSF) was exogenously supplied. Tartrate-resistant acid phosphatase (TRACP; a marker enzyme of osteoclasts)-positive cells appeared only when bone marrow cells were cultured in contact with OP6L7 cells and both rhM-CSF and 1 alpha, 25 (OH)2D3 were added. The TRACP-positive cells became multinucleated with increasing time in culture and expressed the c-fms/M-CSF receptor. These results indicate that both contact with stromal cells and M-CSF are requisite for osteoclast differentiation under physiological conditions.
骨石化(op/op)突变小鼠中破骨细胞、单核细胞和腹膜巨噬细胞的严重缺乏是由于功能性巨噬细胞集落刺激因子(M-CSF)的缺失所致。为了阐明M-CSF在破骨细胞分化中的作用,我们建立了一种能够支持新生op/op小鼠颅骨造血的克隆基质细胞系OP6L7。尽管在骨髓细胞与OP6L7细胞的共培养物中出现的巨噬细胞很少,但当外源性提供纯化的重组人M-CSF(rhM-CSF)时,在第7天的共培养物中检测到的巨噬细胞数量增加了50倍。仅当骨髓细胞与OP6L7细胞接触并添加rhM-CSF和1α,25(OH)2D3时才出现抗酒石酸酸性磷酸酶(TRACP;破骨细胞的标记酶)阳性细胞。随着培养时间的延长,TRACP阳性细胞变成多核并表达c-fms/M-CSF受体。这些结果表明,在生理条件下,与基质细胞的接触和M-CSF对于破骨细胞的分化都是必需的。