Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- Osteolysis
Joint replacement is essential for the treatment of serious joint disease. However, prosthetic failure remains an important clinical issue, with periprosthesis osteolysis (PO), caused by osteoclastic bone resorption induced by wear particles, being the leading cause of failure. Nuclear factor of act...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.01291/full |
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| author | Chuanlong Wu Chuanlong Wu Xuqiang Liu Ruixin Sun Yunhao Qin Zhiqing Liu Shengbing Yang Tingting Tang Zhenan Zhu Degang Yu Fengxiang Liu |
| author_facet | Chuanlong Wu Chuanlong Wu Xuqiang Liu Ruixin Sun Yunhao Qin Zhiqing Liu Shengbing Yang Tingting Tang Zhenan Zhu Degang Yu Fengxiang Liu |
| author_sort | Chuanlong Wu |
| collection | DOAJ |
| description | Joint replacement is essential for the treatment of serious joint disease. However, prosthetic failure remains an important clinical issue, with periprosthesis osteolysis (PO), caused by osteoclastic bone resorption induced by wear particles, being the leading cause of failure. Nuclear factor of activated T cells c1 (NFATc1) appears to play an important role in wear particle-induced osteoclastogenesis, with bicarbonate/chloride exchanger, solute carrier family 4, anion exchanger, member 2, (SLC4A2) being upregulated during osteoclastogenesis in an NFATc1-dependent manner. Anion exchange mediated by SLC4A2 in osteoclasts could affect the bone resorption activity by regulating pHi. This study investigated the role and mechanism of SLC4A2 in wear particle-induced osteoclast differentiation and function in vitro. The use of 4, 4′-diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS), an anion exchange inhibitor, suppressed wear particle-induced PO in vivo. Furthermore, controlled release of DIDS from chitosan microspheres can strengthen the PO therapy effect. Therefore, anion exchange mediated by osteoclastic SLC4A2 may be a potential therapeutic target for the treatment of aseptic loosening of artificial joints. |
| first_indexed | 2024-12-11T11:39:39Z |
| format | Article |
| id | doaj.art-19ed46c2a8fc4de9a1d5aeab37530aec |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T11:39:39Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-19ed46c2a8fc4de9a1d5aeab37530aec2022-12-22T01:08:38ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-11-01910.3389/fphar.2018.01291410280Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- OsteolysisChuanlong Wu0Chuanlong Wu1Xuqiang Liu2Ruixin Sun3Yunhao Qin4Zhiqing Liu5Shengbing Yang6Tingting Tang7Zhenan Zhu8Degang Yu9Fengxiang Liu10Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopaedics, The First Affiliated Hospital, Nanchang University, Nanchang, ChinaState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopaedics, Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaJoint replacement is essential for the treatment of serious joint disease. However, prosthetic failure remains an important clinical issue, with periprosthesis osteolysis (PO), caused by osteoclastic bone resorption induced by wear particles, being the leading cause of failure. Nuclear factor of activated T cells c1 (NFATc1) appears to play an important role in wear particle-induced osteoclastogenesis, with bicarbonate/chloride exchanger, solute carrier family 4, anion exchanger, member 2, (SLC4A2) being upregulated during osteoclastogenesis in an NFATc1-dependent manner. Anion exchange mediated by SLC4A2 in osteoclasts could affect the bone resorption activity by regulating pHi. This study investigated the role and mechanism of SLC4A2 in wear particle-induced osteoclast differentiation and function in vitro. The use of 4, 4′-diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS), an anion exchange inhibitor, suppressed wear particle-induced PO in vivo. Furthermore, controlled release of DIDS from chitosan microspheres can strengthen the PO therapy effect. Therefore, anion exchange mediated by osteoclastic SLC4A2 may be a potential therapeutic target for the treatment of aseptic loosening of artificial joints.https://www.frontiersin.org/article/10.3389/fphar.2018.01291/fullbone resorptionwear particleosteoclastSLC4A2actin |
| spellingShingle | Chuanlong Wu Chuanlong Wu Xuqiang Liu Ruixin Sun Yunhao Qin Zhiqing Liu Shengbing Yang Tingting Tang Zhenan Zhu Degang Yu Fengxiang Liu Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- Osteolysis Frontiers in Pharmacology bone resorption wear particle osteoclast SLC4A2 actin |
| title | Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- Osteolysis |
| title_full | Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- Osteolysis |
| title_fullStr | Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- Osteolysis |
| title_full_unstemmed | Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- Osteolysis |
| title_short | Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- Osteolysis |
| title_sort | targeting anion exchange of osteoclast a new strategy for preventing wear particles induced osteolysis |
| topic | bone resorption wear particle osteoclast SLC4A2 actin |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.01291/full |
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