Role of CXCL10 released from osteocytes in response to TNF-α stimulation on osteoclasts
Abstract Tumor necrosis factor-alpha (TNF-α) is a significant cytokine that regulates bone resorption under inflammatory conditions. However, its mechanism of action in osteocytes remains unclear. In this study, highly purified osteocytes were isolated from dentin matrix protein 1 (DMP1)-Topaz mice...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-87092-7 |
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| author | Mariko Miura Hideki Kitaura Fumitoshi Ohori Kohei Narita Jiayi Ren Takahiro Noguchi Aseel Marahleh Jinghan Ma Angyi Lin Ziqiu Fan Itaru Mizoguchi |
| author_facet | Mariko Miura Hideki Kitaura Fumitoshi Ohori Kohei Narita Jiayi Ren Takahiro Noguchi Aseel Marahleh Jinghan Ma Angyi Lin Ziqiu Fan Itaru Mizoguchi |
| author_sort | Mariko Miura |
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| description | Abstract Tumor necrosis factor-alpha (TNF-α) is a significant cytokine that regulates bone resorption under inflammatory conditions. However, its mechanism of action in osteocytes remains unclear. In this study, highly purified osteocytes were isolated from dentin matrix protein 1 (DMP1)-Topaz mice using cell sorter. RNA sequencing (RNA-seq) revealed that TNF-α stimulation increased C-X-C motif chemokine ligand 10 (CXCL10) gene expression in osteocytes. Although CXCL10 did not affect osteoclast differentiation in vitro, it enhanced the migration of osteoclast precursors. Additionally, in the transwell co-culture system, TNF-α induced the migration of osteoclast precursors. However, this effect was attenuated by a CXCL10-neutralizing antibody. In vivo, mice were administered supracalvarial injections of TNF-α with or without the CXCL10-neutralizing antibody for 5 days. The percentage of CXCL10-positive osteocytes increased after TNF-α administration. Additionally, osteoclast formation and bone resorption were assessed. CXCL10-neutralizing antibody-treated calvariae exhibited a significantly lower number of osteoclasts and bone resorption than those treated with TNF-α alone. These results indicated that TNF-α-induced CXCL10, which affects the migration of osteocyte-derived osteoclast precursors, may enhance TNF-α-triggered osteoclast formation and bone resorption in vivo. |
| format | Article |
| id | doaj-art-ab7888fa554e416191ef833564178d1c |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-ab7888fa554e416191ef833564178d1c2025-01-26T12:25:30ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-87092-7Role of CXCL10 released from osteocytes in response to TNF-α stimulation on osteoclastsMariko Miura0Hideki Kitaura1Fumitoshi Ohori2Kohei Narita3Jiayi Ren4Takahiro Noguchi5Aseel Marahleh6Jinghan Ma7Angyi Lin8Ziqiu Fan9Itaru Mizoguchi10Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryDivision of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of DentistryAbstract Tumor necrosis factor-alpha (TNF-α) is a significant cytokine that regulates bone resorption under inflammatory conditions. However, its mechanism of action in osteocytes remains unclear. In this study, highly purified osteocytes were isolated from dentin matrix protein 1 (DMP1)-Topaz mice using cell sorter. RNA sequencing (RNA-seq) revealed that TNF-α stimulation increased C-X-C motif chemokine ligand 10 (CXCL10) gene expression in osteocytes. Although CXCL10 did not affect osteoclast differentiation in vitro, it enhanced the migration of osteoclast precursors. Additionally, in the transwell co-culture system, TNF-α induced the migration of osteoclast precursors. However, this effect was attenuated by a CXCL10-neutralizing antibody. In vivo, mice were administered supracalvarial injections of TNF-α with or without the CXCL10-neutralizing antibody for 5 days. The percentage of CXCL10-positive osteocytes increased after TNF-α administration. Additionally, osteoclast formation and bone resorption were assessed. CXCL10-neutralizing antibody-treated calvariae exhibited a significantly lower number of osteoclasts and bone resorption than those treated with TNF-α alone. These results indicated that TNF-α-induced CXCL10, which affects the migration of osteocyte-derived osteoclast precursors, may enhance TNF-α-triggered osteoclast formation and bone resorption in vivo.https://doi.org/10.1038/s41598-025-87092-7OsteocyteOsteoclastTNF-αCXCL10Bone resorptionMigration |
| spellingShingle | Mariko Miura Hideki Kitaura Fumitoshi Ohori Kohei Narita Jiayi Ren Takahiro Noguchi Aseel Marahleh Jinghan Ma Angyi Lin Ziqiu Fan Itaru Mizoguchi Role of CXCL10 released from osteocytes in response to TNF-α stimulation on osteoclasts Scientific Reports Osteocyte Osteoclast TNF-α CXCL10 Bone resorption Migration |
| title | Role of CXCL10 released from osteocytes in response to TNF-α stimulation on osteoclasts |
| title_full | Role of CXCL10 released from osteocytes in response to TNF-α stimulation on osteoclasts |
| title_fullStr | Role of CXCL10 released from osteocytes in response to TNF-α stimulation on osteoclasts |
| title_full_unstemmed | Role of CXCL10 released from osteocytes in response to TNF-α stimulation on osteoclasts |
| title_short | Role of CXCL10 released from osteocytes in response to TNF-α stimulation on osteoclasts |
| title_sort | role of cxcl10 released from osteocytes in response to tnf α stimulation on osteoclasts |
| topic | Osteocyte Osteoclast TNF-α CXCL10 Bone resorption Migration |
| url | https://doi.org/10.1038/s41598-025-87092-7 |
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