A stable analogue of throm☐ane A2, 9,11-epithio-11,12-methanothrom☐ane A2, stimulates bone resorption in vitro and osteoclast-like cell formation in mouse marrow culture
| Autor: | Ken-ichi Yamasaki, Shoji Yamada, Tatsuo Fukuhara, Takuhiko Akatsu, Naoyuki Takahashi, Yoshinobu Shibasaki, Akira Matsumoto, Tatsuo Suda, Shigeru Saito |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Male
musculoskeletal diseases medicine.medical_specialty Indomethacin Osteoclasts Bone Marrow Cells Biology Biochemistry Bone and Bones Dinoprostone Bone resorption Mice Thromboxane A2 chemistry.chemical_compound Endocrinology Bone Marrow Osteoclast Culture Techniques Internal medicine medicine Animals Bone Resorption Prostaglandin E2 Dose-Response Relationship Drug Calcium Radioisotopes Smooth muscle contraction Resorption Thromboxane B2 Kinetics medicine.anatomical_structure chemistry lipids (amino acids peptides and proteins) Surgery Bone marrow circulatory and respiratory physiology medicine.drug |
| Zdroj: | Bone and Mineral. 12:15-23 |
| ISSN: | 0169-6009 |
| DOI: | 10.1016/0169-6009(91)90118-j |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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