Saito S, Yamasaki K, Yamada S, Matsumoto A, Akatsu T, Takahashi N, Shibasaki Y, Suda T, Fukuhara T
Department of Orthodontics, School of Dentistry, Showa University, Tokyo, Japan.
Bone Miner. 1991 Jan;12(1):15-23. doi: 10.1016/0169-6009(91)90118-j.
Thromboxane A2 (TXA2) is a powerful promoter of platelet aggregation and smooth muscle contraction. However, this compound is highly unstable and is rapidly hydrated to a more stable metabolite, thromboxane B2 (TXB2). TXA2 has been considered to be involved in bone resorption, in particular bone loss caused by inflammatory diseases and by orthodontic treatment. However precise mechanisms of bone resorption caused by TXA2 have not yet been proved because of its highly unstable nature. Recently, a chemically stable analogue of TXA2, 9,11-epithio-11,12-methanothromboxane A2 (STA2), was successfully synthesized. Using this synthetic compound, we examined its in vitro bone resorbing activity and induction of osteoclast-like cells in a mouse marrow culture system in comparison with related compounds with bone resorbing activity. Like prostaglandin E2 (PGE2), a well-known bone resorbing agent, STA2 time- and dose-dependently stimulated the release of 45Ca from prelabelled mouse calvariae. Both STA2 and PGE2 induced the accumulation of cAMP in mouse calvariae. The TXA2 antagonist, ONO-3708, inhibited STA2-induced release of 45Ca. TXB2 induced neither bone resorption nor cAMP accumulation. When mouse marrow cells were cultured with STA2 for 8 days, osteoclast-like multinucleated cells appeared in parallel with the increase of the amount of STA2 added. Again TXB2 showed no effect on osteoclast-like cell formation. These results indicate a role for TXA2 in some form of bone resorption.
血栓素A2（TXA2）是血小板聚集和平滑肌收缩的强效促进剂。然而，这种化合物极不稳定，会迅速水合形成更稳定的代谢产物血栓素B2（TXB2）。TXA2被认为与骨吸收有关，特别是与炎症性疾病和正畸治疗引起的骨质流失有关。然而，由于TXA2性质极不稳定，其导致骨吸收的确切机制尚未得到证实。最近，成功合成了一种化学性质稳定的TXA2类似物，即9,11-环氧-11,12-甲撑血栓素A2（STA2）。利用这种合成化合物，我们在小鼠骨髓培养系统中，与具有骨吸收活性的相关化合物相比，检测了其体外骨吸收活性以及破骨细胞样细胞的诱导情况。与众所周知的骨吸收剂前列腺素E2（PGE2）一样，STA2能时间和剂量依赖性地刺激预先标记的小鼠颅骨释放45Ca。STA2和PGE2均能诱导小鼠颅骨中cAMP的积累。TXA2拮抗剂ONO-3708可抑制STA2诱导的45Ca释放。TXB2既不诱导骨吸收，也不诱导cAMP积累。当小鼠骨髓细胞与STA2培养8天时，破骨细胞样多核细胞出现，且与添加的STA2量的增加平行。同样，TXB2对破骨细胞样细胞的形成没有影响。这些结果表明TXA2在某种形式的骨吸收中发挥作用。
