Ljunggren O, Ljunghall S
Department of Internal Medicine, University Hospital, Uppsala, Sweden.
Biochem Biophys Res Commun. 1993 Jun 30;193(3):821-6. doi: 10.1006/bbrc.1993.1699.
Stimulation of osteoclastic bone resorption is mediated via the osteoblasts. In order to investigate the second messenger events that cause the osteoblasts to initiate bone resorption we have evaluated the effect of the cyclic AMP antagonist adenosine-3'5'-cyclic monophosphosphorothioate, Rp-isomer (Rp-cAMPS) on bone resorption in vitro, by measuring the release of prelabelled 45Ca from cultured neonatal mouse calvarial bones. Forskolin (FSK, at and above 10 nM), an agent that enhances cyclic AMP-formation, stimulated bone resorption in 96 h cultures. Addition of Rp-cAMPS to the incubation media dose-dependently inhibited bone resorption induced by FSK (0.5 microM), with total inhibition obtained at 30 microM Rp-cAMPS. Bone resorption stimulated by parathyroid hormone (PTH, 0.1-10 nM, 72 h) was also inhibited by Rp-cAMPS (30 microM), while bone resorption induced by 1.25(OH)2D3 (1-10 nM, 72 h) was unaffected by Rp-cAMPS. These data demonstrate that PTH and 1,25(OH)2D3 cause bone resorption via different mechanisms and that cyclic AMP is the major second messenger in PTH-induced bone resorption.
破骨细胞性骨吸收的刺激是通过成骨细胞介导的。为了研究导致成骨细胞启动骨吸收的第二信使事件，我们通过测量培养的新生小鼠颅骨中预标记的45Ca的释放，评估了环磷酸腺苷拮抗剂3',5'-环磷硫腺苷，Rp-异构体（Rp-cAMPS）对体外骨吸收的影响。福斯高林（FSK，10 nM及以上）是一种增强环磷酸腺苷形成的药物，在96小时培养中刺激骨吸收。向孵育培养基中添加Rp-cAMPS剂量依赖性地抑制了FSK（0.5 microM）诱导的骨吸收，在30 microM Rp-cAMPS时获得完全抑制。甲状旁腺激素（PTH，0.1 - 10 nM，72小时）刺激的骨吸收也被Rp-cAMPS（30 microM）抑制，而1,25(OH)2D3（1 - 10 nM，72小时）诱导的骨吸收不受Rp-cAMPS影响。这些数据表明，PTH和1,25(OH)2D3通过不同机制引起骨吸收，并且环磷酸腺苷是PTH诱导的骨吸收中的主要第二信使。
