TNFα stimulates osteoclastogenesis and expression of CX3CL1 in non-adherent bone marrow cells
The balance between bone formation by osteoblasts and bone resorption by osteoclasts is a critical step in maintaining bone homeostasis. Excessive activation of osteoclasts is important in the bone destruction seen in diseases such as osteoporosis and rheumatoid arthritis. The microenvironment aroun...
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| Language: | English |
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Elsevier
2025-09-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825002420 |
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| author | Yuto Otsuka Narumi Hattori Hiromasa Aoki Kohki Toriuchi Yasumichi Inoue Hidetoshi Hayashi Gen Kuroyanagi Yohei Kawaguchi Yuko Waguri-Nagaya Mineyoshi Aoyama |
| author_facet | Yuto Otsuka Narumi Hattori Hiromasa Aoki Kohki Toriuchi Yasumichi Inoue Hidetoshi Hayashi Gen Kuroyanagi Yohei Kawaguchi Yuko Waguri-Nagaya Mineyoshi Aoyama |
| author_sort | Yuto Otsuka |
| collection | DOAJ |
| description | The balance between bone formation by osteoblasts and bone resorption by osteoclasts is a critical step in maintaining bone homeostasis. Excessive activation of osteoclasts is important in the bone destruction seen in diseases such as osteoporosis and rheumatoid arthritis. The microenvironment around bone marrow cells regulates osteoclastogenesis through cytokine expression. Tumor necrosis factor–α (TNFα) is a proinflammatory cytokine that plays an important role in bone loss in rheumatoid arthritis. Therefore, this study investigated the effect of TNFα on osteoclastogenesis via chemokines produced by microenvironmental cells. In in vitro culture of mouse bone marrow cells, TNFα added simultaneously with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) from the initiation of culture significantly inhibited osteoclast formation. By contrast, TNFα stimulation from 7 days after prior stimulation with RANKL and M-CSF significantly promoted osteoclastogenesis. This late-stage promotional effect was associated with the upregulation in non-adherent bone marrow cells of C-X3-C motif chemokine ligand 1 (CX3CL1) and C-X-C motif ligand 7 (CXCL7), which are potent chemoattractant and adhesion molecules. Neutralizing antibodies against TNF receptor 1 (TNFR1) and TNFR2 markedly suppressed osteoclastogenesis in the presence of TNFα. Additionally, these antibodies significantly reduced CX3CL1—but not CXCL7—mRNA expression levels in non-adherent bone marrow cells. In conclusion, our results suggest that TNFα treatment in the late stage promotes osteoclast formation and increases the expression of CX3CL1 in non-adherent bone marrow cells. These findings highlight the time-dependent role of TNFα in osteoclastogenesis relative to non-adherent bone marrow cells. |
| format | Article |
| id | doaj-art-e72a81398b344540a19f5565ad5ef652 |
| institution | Kabale University |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-e72a81398b344540a19f5565ad5ef6522025-08-20T03:50:22ZengElsevierBiochemistry and Biophysics Reports2405-58082025-09-014310215510.1016/j.bbrep.2025.102155TNFα stimulates osteoclastogenesis and expression of CX3CL1 in non-adherent bone marrow cellsYuto Otsuka0Narumi Hattori1Hiromasa Aoki2Kohki Toriuchi3Yasumichi Inoue4Hidetoshi Hayashi5Gen Kuroyanagi6Yohei Kawaguchi7Yuko Waguri-Nagaya8Mineyoshi Aoyama9Department of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, JapanDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, JapanDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, JapanDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, JapanDepartment of Cell Signaling, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan; Department of Innovative Therapeutic Sciences, Cooperative Major in Nanopharmaceutical Sciences, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi, 467-8603, JapanDepartment of Cell Signaling, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan; Department of Innovative Therapeutic Sciences, Cooperative Major in Nanopharmaceutical Sciences, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi, 467-8603, JapanDepartment of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, JapanDepartment of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, JapanDepartment of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, JapanDepartment of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan; Corresponding author.The balance between bone formation by osteoblasts and bone resorption by osteoclasts is a critical step in maintaining bone homeostasis. Excessive activation of osteoclasts is important in the bone destruction seen in diseases such as osteoporosis and rheumatoid arthritis. The microenvironment around bone marrow cells regulates osteoclastogenesis through cytokine expression. Tumor necrosis factor–α (TNFα) is a proinflammatory cytokine that plays an important role in bone loss in rheumatoid arthritis. Therefore, this study investigated the effect of TNFα on osteoclastogenesis via chemokines produced by microenvironmental cells. In in vitro culture of mouse bone marrow cells, TNFα added simultaneously with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) from the initiation of culture significantly inhibited osteoclast formation. By contrast, TNFα stimulation from 7 days after prior stimulation with RANKL and M-CSF significantly promoted osteoclastogenesis. This late-stage promotional effect was associated with the upregulation in non-adherent bone marrow cells of C-X3-C motif chemokine ligand 1 (CX3CL1) and C-X-C motif ligand 7 (CXCL7), which are potent chemoattractant and adhesion molecules. Neutralizing antibodies against TNF receptor 1 (TNFR1) and TNFR2 markedly suppressed osteoclastogenesis in the presence of TNFα. Additionally, these antibodies significantly reduced CX3CL1—but not CXCL7—mRNA expression levels in non-adherent bone marrow cells. In conclusion, our results suggest that TNFα treatment in the late stage promotes osteoclast formation and increases the expression of CX3CL1 in non-adherent bone marrow cells. These findings highlight the time-dependent role of TNFα in osteoclastogenesis relative to non-adherent bone marrow cells.http://www.sciencedirect.com/science/article/pii/S2405580825002420OsteoclastTNFαChemokineMicroenvironmentRheumatoid arthritis |
| spellingShingle | Yuto Otsuka Narumi Hattori Hiromasa Aoki Kohki Toriuchi Yasumichi Inoue Hidetoshi Hayashi Gen Kuroyanagi Yohei Kawaguchi Yuko Waguri-Nagaya Mineyoshi Aoyama TNFα stimulates osteoclastogenesis and expression of CX3CL1 in non-adherent bone marrow cells Biochemistry and Biophysics Reports Osteoclast TNFα Chemokine Microenvironment Rheumatoid arthritis |
| title | TNFα stimulates osteoclastogenesis and expression of CX3CL1 in non-adherent bone marrow cells |
| title_full | TNFα stimulates osteoclastogenesis and expression of CX3CL1 in non-adherent bone marrow cells |
| title_fullStr | TNFα stimulates osteoclastogenesis and expression of CX3CL1 in non-adherent bone marrow cells |
| title_full_unstemmed | TNFα stimulates osteoclastogenesis and expression of CX3CL1 in non-adherent bone marrow cells |
| title_short | TNFα stimulates osteoclastogenesis and expression of CX3CL1 in non-adherent bone marrow cells |
| title_sort | tnfα stimulates osteoclastogenesis and expression of cx3cl1 in non adherent bone marrow cells |
| topic | Osteoclast TNFα Chemokine Microenvironment Rheumatoid arthritis |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825002420 |
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