Quinn J M, Sabokbar A, Denne M, de Vernejoul M C, McGee J O, Athanasou N A
Nuffield Department of Pathology, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom.
Calcif Tissue Int. 1997 Jan;60(1):63-70. doi: 10.1007/s002239900187.
The effect of prostaglandins (PGs) on osteoclast differentiation, an important point of control for bone resorption, is poorly understood. After an initial differentiation phase that lasts at least 4 days, murine monocytes, cocultured with UMR106 osteoblastic cells (in the presence of 1,25-dihydroxyvitamin D3) give rise to tartrate-resistant acid phosphatase (TRAP) positive osteoclast-like cells that are capable of lacunar bone resorption. PGE2 strongly inhibits TRAP expression and bone resorption in these cocultures. To examine further the cellular mechanisms associated with this inhibitory effect, we added PGE2 to monocyte/UMR106 cocultures at specific times before, during, and after this initial 4-day differentiation period. To determine whether this PGE2 inhibition was dependent on the type of stromal cell supporting osteoclast differentiation, we also added PGE2 to cocultures of monocytes with ST2 preadipocytic cells. Inhibition of bone resorption was greatly reduced when the addition of PGE2 to monocyte/UMR106 cocultures was delayed until the fourth day of incubation; when delayed until the seventh day, inhibition did not occur. PGE2 inhibition of bone resorption was concentration-dependent and at 10(-6) M was also mediated by PGE1 and PGF2alpha. In contrast to its effects on monocyte/UMR106 cocultures, PGE2 stimulated bone resorption in monocyte/ST2 cocultures. Both ST2 cells and UMR106 cells were shown to express functional receptors for PGE2.These results show that PGs strongly influence the differentiation of osteoclast precursors and that this effect is dependent not only on the type and dose of PG administered, but also on the nature of the bone-derived stromal cell supporting this process.
前列腺素（PGs）对破骨细胞分化（骨吸收的一个重要控制点）的影响尚不清楚。在持续至少4天的初始分化阶段后，与UMR106成骨细胞共培养（在1,25 - 二羟维生素D3存在下）的小鼠单核细胞会产生抗酒石酸酸性磷酸酶（TRAP）阳性的破骨细胞样细胞，这些细胞能够进行腔隙性骨吸收。PGE2强烈抑制这些共培养物中TRAP的表达和骨吸收。为了进一步研究与这种抑制作用相关的细胞机制，我们在最初4天的分化期之前、期间和之后的特定时间向单核细胞/UMR106共培养物中添加PGE2。为了确定这种PGE2抑制是否依赖于支持破骨细胞分化的基质细胞类型，我们还向单核细胞与ST2前脂肪细胞的共培养物中添加PGE2。当向单核细胞/UMR106共培养物中添加PGE2推迟到培养的第四天时，骨吸收的抑制作用大大降低；当推迟到第七天时，抑制作用未出现。PGE2对骨吸收的抑制作用是浓度依赖性的，在10(-6) M时，PGE1和PGF2α也介导这种抑制作用。与它对单核细胞/UMR106共培养物的作用相反，PGE2刺激单核细胞/ST2共培养物中的骨吸收。ST2细胞和UMR106细胞都被证明表达功能性的PGE2受体。这些结果表明，PGs强烈影响破骨细胞前体的分化，并且这种作用不仅取决于所施用的PG的类型和剂量，还取决于支持这一过程的骨源性基质细胞的性质。
