Dual role of phosphatidylserine and its receptors in osteoclastogenesis
| العنوان: | Dual role of phosphatidylserine and its receptors in osteoclastogenesis |
|---|---|
| المؤلفون: | Geum-Dong Han, Su-Young Lee, Sun-Hun Kim, Jee-Hae Kang, Jeong-Tae Koh, Hyun-Mi Ko, Min-Seok Kim, Jung-Sun Moon |
| المصدر: | Cell Death & Disease Cell Death and Disease, Vol 11, Iss 7, Pp 1-11 (2020) |
| بيانات النشر: | Nature Publishing Group UK, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Cell biology, Molecular biology, Immunology, Osteoclasts, Apoptosis, Bone Marrow Cells, Receptors, Cell Surface, Phosphatidylserines, Giant Cells, Article, Exocytosis, Cell Fusion, Rats, Sprague-Dawley, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Multinucleate, Adenosine Triphosphate, Downregulation and upregulation, Osteoclast, Osteogenesis, medicine, Alveolar Process, Animals, lcsh:QH573-671, Receptor, ATP Binding Cassette Transporter, Subfamily G, Member 1, Adenosine Triphosphatases, 030102 biochemistry & molecular biology, biology, lcsh:Cytology, Tartrate-Resistant Acid Phosphatase, CD47, Tooth Germ, Phosphatidylserine, Dendritic Cells, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, chemistry, Animals, Newborn, RANKL, biology.protein, Multidrug Resistance-Associated Proteins |
| الوصف: | Fusion and apoptosis share a breakdown of the membrane phospholipids asymmetry, modes of which are largely unknown in osteoclastogenesis. Here, we investigated the externalization of phosphatidylserine (PS) and its receptors, and their biological functions in osteoclastogenesis. Strong immunoreactivities in vivo for the PS receptors TIM4, BAI1, and STAB2 were observed in the TRAP-positive multinucleated cells in the alveolar bone that was being remodeled around the developing dental follicles in rats. These receptors were significantly upregulated during M-CSF/RANKL-induced in vitro osteoclastogenesis using mouse bone marrow-derived cells. PS externalization in preosteoclasts was increased by the M-CSF/RANKL treatment. Multinucleation of preosteoclasts was markedly inhibited by antibodies against PS and its receptors. Among the investigated lipid transporter proteins, floppases (Abcb4, Abcc5, and Abcg1) were upregulated, whereas flippases (Atp11c and Atp8a1) downregulated during osteoclastogenesis. Preosteoclast fusion was markedly blocked by the ATPase inhibitor Na3VO4 and siRNAs against Abcc5 and Abcg1, revealing the importance of these lipid transporters in PS externalization. Further, the levels of Cd47 and Cd31, don’t-eat-me signal inducers, were increased or sustained in the early phase of osteoclastogenesis, whereas those of AnnexinI and Mfg-e8, eat-me signals inducers, were increased in the late apoptotic phase. In addition, Z-VAD-FMK, a pan caspase inhibitor, had no effect on preosteoclast fusion in the early phase of osteoclastogenesis, whereas Abs against PS, TIM4, and BAI1 decreased osteoclast apoptosis during the late phase. These results suggest that PS externalization is essential for the whole process of osteoclastogenesis and share PS receptors and transporters in the early stage fusion and late stage apoptosis. Therefore, modulation of PS and its receptors could be a useful strategy to develop anti-bone resorptive agents. |
| اللغة: | English |
| تدمد: | 2041-4889 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bfc8718664e73b318d320d36a1c7159e http://europepmc.org/articles/PMC7330034 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bfc8718664e73b318d320d36a1c7159e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
|---|