Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts
Abstract Background Long-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated p...
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BMC
2023-05-01
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| Series: | BMC Oral Health |
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| Online Access: | https://doi.org/10.1186/s12903-023-03034-7 |
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| author | Ning Zhao Qing-xiang Li Yi-fei Wang Qiao Qiao Hong-yuan Huang Chuan-bin Guo Yu-xing Guo |
| author_facet | Ning Zhao Qing-xiang Li Yi-fei Wang Qiao Qiao Hong-yuan Huang Chuan-bin Guo Yu-xing Guo |
| author_sort | Ning Zhao |
| collection | DOAJ |
| description | Abstract Background Long-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated patients. Methods The clinical stage and jawbone exposure of MRONJ patients caused by different drug regimens were analyzed to ascertain the aggravation effect of anti-angiogenic drugs on anti-resorptive drug-based MRONJ. Next, a periodontitis mice model was established, and tooth extraction was performed after administering anti-resorptive and/or anti-angiogenic drugs; the imaging and histological change of the extraction socket were observed. Moreover, the cell function of gingival fibroblasts was analyzed after the treatment with anti-resorptive and/or anti-angiogenic drugs in order to evaluate their effect on the gingival tissue healing of the extraction socket. Results Patients treated with anti-angiogenic and anti-resorptive drugs had an advanced clinical stage and a bigger proportion of necrotic jawbone exposure compared to patients treated with anti-resorptive drugs alone. In vivo study further indicated a greater loss of mucosa tissue coverage above the tooth extraction in mice treated with sunitinib (Suti) + zoledronate (Zole) group (7/10) vs. Zole group (3/10) and Suti group (1/10). Micro-computed tomography (CT) and histological data showed that the new bone formation in the extraction socket was lower in Suti + Zole and Zole groups vs. Suti and control groups. In vitro data showed that the anti-angiogenic drugs had a stronger inhibitory ability on the proliferation and migration function of gingival fibroblasts than anti-resorptive drugs, and the inhibitory effect was obviously enhanced after combining zoledronate and sunitinib. Conclusion Our findings provided support for a synergistic contribution of anti-angiogenic drugs to anti-resorptive drugs-based MRONJ. Importantly, the present study revealed that anti-angiogenic drugs alone do not induce severe MRONJ but aggravate the degree of MRONJ via the enhanced inhibitory function of gingival fibroblasts based on anti-resorptive drugs. |
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| format | Article |
| id | doaj.art-b38decf54f7e431d83c7c5fab809b33a |
| institution | Directory Open Access Journal |
| issn | 1472-6831 |
| language | English |
| last_indexed | 2024-03-13T08:58:43Z |
| publishDate | 2023-05-01 |
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| series | BMC Oral Health |
| spelling | doaj.art-b38decf54f7e431d83c7c5fab809b33a2023-05-28T11:29:22ZengBMCBMC Oral Health1472-68312023-05-0123111110.1186/s12903-023-03034-7Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblastsNing Zhao0Qing-xiang Li1Yi-fei Wang2Qiao Qiao3Hong-yuan Huang4Chuan-bin Guo5Yu-xing Guo6Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of StomatologyAbstract Background Long-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated patients. Methods The clinical stage and jawbone exposure of MRONJ patients caused by different drug regimens were analyzed to ascertain the aggravation effect of anti-angiogenic drugs on anti-resorptive drug-based MRONJ. Next, a periodontitis mice model was established, and tooth extraction was performed after administering anti-resorptive and/or anti-angiogenic drugs; the imaging and histological change of the extraction socket were observed. Moreover, the cell function of gingival fibroblasts was analyzed after the treatment with anti-resorptive and/or anti-angiogenic drugs in order to evaluate their effect on the gingival tissue healing of the extraction socket. Results Patients treated with anti-angiogenic and anti-resorptive drugs had an advanced clinical stage and a bigger proportion of necrotic jawbone exposure compared to patients treated with anti-resorptive drugs alone. In vivo study further indicated a greater loss of mucosa tissue coverage above the tooth extraction in mice treated with sunitinib (Suti) + zoledronate (Zole) group (7/10) vs. Zole group (3/10) and Suti group (1/10). Micro-computed tomography (CT) and histological data showed that the new bone formation in the extraction socket was lower in Suti + Zole and Zole groups vs. Suti and control groups. In vitro data showed that the anti-angiogenic drugs had a stronger inhibitory ability on the proliferation and migration function of gingival fibroblasts than anti-resorptive drugs, and the inhibitory effect was obviously enhanced after combining zoledronate and sunitinib. Conclusion Our findings provided support for a synergistic contribution of anti-angiogenic drugs to anti-resorptive drugs-based MRONJ. Importantly, the present study revealed that anti-angiogenic drugs alone do not induce severe MRONJ but aggravate the degree of MRONJ via the enhanced inhibitory function of gingival fibroblasts based on anti-resorptive drugs.https://doi.org/10.1186/s12903-023-03034-7Anti-angiogenicAnti-resorptiveMedication-related osteonecrosis of the jawGingival fibroblastsProliferation and migration |
| spellingShingle | Ning Zhao Qing-xiang Li Yi-fei Wang Qiao Qiao Hong-yuan Huang Chuan-bin Guo Yu-xing Guo Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts BMC Oral Health Anti-angiogenic Anti-resorptive Medication-related osteonecrosis of the jaw Gingival fibroblasts Proliferation and migration |
| title | Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts |
| title_full | Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts |
| title_fullStr | Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts |
| title_full_unstemmed | Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts |
| title_short | Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts |
| title_sort | anti angiogenic drug aggravates the degree of anti resorptive drug based medication related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts |
| topic | Anti-angiogenic Anti-resorptive Medication-related osteonecrosis of the jaw Gingival fibroblasts Proliferation and migration |
| url | https://doi.org/10.1186/s12903-023-03034-7 |
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