Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing
Abstract Background Medication-related osteonecrosis of the jaw (MRONJ) is a serious debilitating disease caused by anti-resorption and anti-angiogenesis drugs, significantly affecting patients' quality of life. Recent studies suggested that primary gingival wound healing may effectively preven...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | BMC Oral Health |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12903-022-02678-1 |
| _version_ | 1797952388918673408 |
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| author | Yi Zheng Xian Dong Shuo Chen Yang He Jingang An Meng Liu Linhai He Yi Zhang |
| author_facet | Yi Zheng Xian Dong Shuo Chen Yang He Jingang An Meng Liu Linhai He Yi Zhang |
| author_sort | Yi Zheng |
| collection | DOAJ |
| description | Abstract Background Medication-related osteonecrosis of the jaw (MRONJ) is a serious debilitating disease caused by anti-resorption and anti-angiogenesis drugs, significantly affecting patients' quality of life. Recent studies suggested that primary gingival wound healing may effectively prevent the development of MRONJ. This study aimed to evaluate the effects of low-level light therapy (LLLT) on promoting gingival wound healing in extraction sockets of MRONJ-like mice and preventing the occurrence of MRONJ. Furthermore, we explored underlying mechanisms. Methods Mice were randomly divided into the Ctrl, Zol, and Zol + LLLT groups. Administration of zoledronate and tooth extraction of bilateral maxillary second molars were used to build the MRONJ model, and LLLT was locally administered into the tooth sockets to examine the effect of LLLT. Next, to explore the function of IL-1RA, we performed LLLT with interleukin-1 receptor antagonist (IL-1RA) neutralizing antibody (named Zol + LLLT + IL-1RA NAb group) or negative control antibodies for tooth extraction in subsequent rescue animal experiments. Stereoscope observations, micro-computed tomography, and histological examination were conducted to evaluate gingival wound healing and bone regeneration in tooth sockets. The effects of LLLT on the migration capacities of zoledronate-treated epithelial cells were assessed in vitro. Results LLLT promoted primary gingival wound healing without exposed necrotic bone. Micro-computed tomography results showed higher bone volume and mineral density of the tooth sockets after LLLT. Histology analysis showed complete gingival coverage, obvious bone regeneration, and reduced soft tissue inflammation, with down-regulated pro-inflammation cytokines, like interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α), and up-regulated IL-1RA expression in the gingival tissue in the LLLT group. The rescue assay further showed that the effects of LLLT promoting gingival wound healing and preventing MRONJ might be partially abolished by IL-1RA neutralizing antibodies. In vitro studies demonstrated that LLLT accelerated zoledronate-treated epithelial cell migration. Conclusions LLLT might promote primary gingival wound healing and contribute to subsequent bone regeneration of the tooth extractions in MRONJ-like lesions via IL-1RA-mediated pro-inflammation signaling suppression. |
| first_indexed | 2024-04-10T22:45:33Z |
| format | Article |
| id | doaj.art-fe0192017d454de39f04ee31515ad402 |
| institution | Directory Open Access Journal |
| issn | 1472-6831 |
| language | English |
| last_indexed | 2024-04-10T22:45:33Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Oral Health |
| spelling | doaj.art-fe0192017d454de39f04ee31515ad4022023-01-15T12:23:02ZengBMCBMC Oral Health1472-68312023-01-0123111410.1186/s12903-022-02678-1Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healingYi Zheng0Xian Dong1Shuo Chen2Yang He3Jingang An4Meng Liu5Linhai He6Yi Zhang7Department 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 StomatologyLaser and Cosmetic Surgery Division, 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 Medication-related osteonecrosis of the jaw (MRONJ) is a serious debilitating disease caused by anti-resorption and anti-angiogenesis drugs, significantly affecting patients' quality of life. Recent studies suggested that primary gingival wound healing may effectively prevent the development of MRONJ. This study aimed to evaluate the effects of low-level light therapy (LLLT) on promoting gingival wound healing in extraction sockets of MRONJ-like mice and preventing the occurrence of MRONJ. Furthermore, we explored underlying mechanisms. Methods Mice were randomly divided into the Ctrl, Zol, and Zol + LLLT groups. Administration of zoledronate and tooth extraction of bilateral maxillary second molars were used to build the MRONJ model, and LLLT was locally administered into the tooth sockets to examine the effect of LLLT. Next, to explore the function of IL-1RA, we performed LLLT with interleukin-1 receptor antagonist (IL-1RA) neutralizing antibody (named Zol + LLLT + IL-1RA NAb group) or negative control antibodies for tooth extraction in subsequent rescue animal experiments. Stereoscope observations, micro-computed tomography, and histological examination were conducted to evaluate gingival wound healing and bone regeneration in tooth sockets. The effects of LLLT on the migration capacities of zoledronate-treated epithelial cells were assessed in vitro. Results LLLT promoted primary gingival wound healing without exposed necrotic bone. Micro-computed tomography results showed higher bone volume and mineral density of the tooth sockets after LLLT. Histology analysis showed complete gingival coverage, obvious bone regeneration, and reduced soft tissue inflammation, with down-regulated pro-inflammation cytokines, like interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α), and up-regulated IL-1RA expression in the gingival tissue in the LLLT group. The rescue assay further showed that the effects of LLLT promoting gingival wound healing and preventing MRONJ might be partially abolished by IL-1RA neutralizing antibodies. In vitro studies demonstrated that LLLT accelerated zoledronate-treated epithelial cell migration. Conclusions LLLT might promote primary gingival wound healing and contribute to subsequent bone regeneration of the tooth extractions in MRONJ-like lesions via IL-1RA-mediated pro-inflammation signaling suppression.https://doi.org/10.1186/s12903-022-02678-1Medication-related osteonecrosis of the jawZoledronateLow-level light therapyInterleukin-1 receptor antagonistInterleukin-1 betaTumor necrosis factor-α |
| spellingShingle | Yi Zheng Xian Dong Shuo Chen Yang He Jingang An Meng Liu Linhai He Yi Zhang Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing BMC Oral Health Medication-related osteonecrosis of the jaw Zoledronate Low-level light therapy Interleukin-1 receptor antagonist Interleukin-1 beta Tumor necrosis factor-α |
| title | Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing |
| title_full | Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing |
| title_fullStr | Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing |
| title_full_unstemmed | Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing |
| title_short | Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing |
| title_sort | low level laser therapy prevents medication related osteonecrosis of the jaw like lesions via il 1ra mediated primary gingival wound healing |
| topic | Medication-related osteonecrosis of the jaw Zoledronate Low-level light therapy Interleukin-1 receptor antagonist Interleukin-1 beta Tumor necrosis factor-α |
| url | https://doi.org/10.1186/s12903-022-02678-1 |
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