PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products
Abstract Osteoblast apoptosis plays an important role in age-related bone loss and osteoporosis. Our previous study revealed that advanced oxidation protein products (AOPPs) could induce nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) production, cause...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-02-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-05595-5 |
| _version_ | 1811165721562972160 |
|---|---|
| author | Wei Li Wang-Sheng Jiang Ya-Ru Su Ke-Wu Tu Lin Zou Cong-Rui Liao Qian Wu Zi-Han Wang Zhao-Ming Zhong Jian-Ting Chen Si-Yuan Zhu |
| author_facet | Wei Li Wang-Sheng Jiang Ya-Ru Su Ke-Wu Tu Lin Zou Cong-Rui Liao Qian Wu Zi-Han Wang Zhao-Ming Zhong Jian-Ting Chen Si-Yuan Zhu |
| author_sort | Wei Li |
| collection | DOAJ |
| description | Abstract Osteoblast apoptosis plays an important role in age-related bone loss and osteoporosis. Our previous study revealed that advanced oxidation protein products (AOPPs) could induce nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) production, cause mitochondrial membrane potential (ΔΨm) depolarization, trigger the mitochondria-dependent intrinsic apoptosis pathway, and lead to osteoblast apoptosis and ultimately osteopenia and bone microstructural destruction. In this study, we found that AOPPs also induced mitochondrial ROS (mtROS) generation in osteoblastic MC3T3-E1 cells, which was closely related to NOX-derived ROS, and aggravated the oxidative stress condition, thereby further promoting apoptosis. Removing excessive ROS and damaged mitochondria is the key factor in reversing AOPP-induced apoptosis. Here, by in vitro studies, we showed that rapamycin further activated PINK1/Parkin-mediated mitophagy in AOPP-stimulated MC3T3-E1 cells and significantly alleviated AOPP-induced cell apoptosis by eliminating ROS and damaged mitochondria. Our in vivo studies revealed that PINK1/Parkin-mediated mitophagy could decrease the plasma AOPP concentration and inhibit AOPP-induced osteoblast apoptosis, thus ameliorating AOPP accumulation-related bone loss, bone microstructural destruction and bone mineral density (BMD) loss. Together, our study indicated that therapeutic strategies aimed at upregulating osteoblast mitophagy and preserving mitochondrial function might have potential for treating age-related osteoporosis. |
| first_indexed | 2024-04-10T15:41:16Z |
| format | Article |
| id | doaj.art-b05134c2af3d49e8989109cbf6b43ef0 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-10T15:41:16Z |
| publishDate | 2023-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-b05134c2af3d49e8989109cbf6b43ef02023-02-12T12:24:02ZengNature Publishing GroupCell Death and Disease2041-48892023-02-0114211210.1038/s41419-023-05595-5PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein productsWei Li0Wang-Sheng Jiang1Ya-Ru Su2Ke-Wu Tu3Lin Zou4Cong-Rui Liao5Qian Wu6Zi-Han Wang7Zhao-Ming Zhong8Jian-Ting Chen9Si-Yuan Zhu10Division of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical UniversityDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical UniversityDepartment of Ophthalmology, Nanfang Hospital, Southern Medical UniversityDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical UniversityDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical UniversityDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical UniversityDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical UniversityDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical UniversityDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical UniversityDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical UniversityDivision of Spine Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical UniversityAbstract Osteoblast apoptosis plays an important role in age-related bone loss and osteoporosis. Our previous study revealed that advanced oxidation protein products (AOPPs) could induce nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) production, cause mitochondrial membrane potential (ΔΨm) depolarization, trigger the mitochondria-dependent intrinsic apoptosis pathway, and lead to osteoblast apoptosis and ultimately osteopenia and bone microstructural destruction. In this study, we found that AOPPs also induced mitochondrial ROS (mtROS) generation in osteoblastic MC3T3-E1 cells, which was closely related to NOX-derived ROS, and aggravated the oxidative stress condition, thereby further promoting apoptosis. Removing excessive ROS and damaged mitochondria is the key factor in reversing AOPP-induced apoptosis. Here, by in vitro studies, we showed that rapamycin further activated PINK1/Parkin-mediated mitophagy in AOPP-stimulated MC3T3-E1 cells and significantly alleviated AOPP-induced cell apoptosis by eliminating ROS and damaged mitochondria. Our in vivo studies revealed that PINK1/Parkin-mediated mitophagy could decrease the plasma AOPP concentration and inhibit AOPP-induced osteoblast apoptosis, thus ameliorating AOPP accumulation-related bone loss, bone microstructural destruction and bone mineral density (BMD) loss. Together, our study indicated that therapeutic strategies aimed at upregulating osteoblast mitophagy and preserving mitochondrial function might have potential for treating age-related osteoporosis.https://doi.org/10.1038/s41419-023-05595-5 |
| spellingShingle | Wei Li Wang-Sheng Jiang Ya-Ru Su Ke-Wu Tu Lin Zou Cong-Rui Liao Qian Wu Zi-Han Wang Zhao-Ming Zhong Jian-Ting Chen Si-Yuan Zhu PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products Cell Death and Disease |
| title | PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products |
| title_full | PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products |
| title_fullStr | PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products |
| title_full_unstemmed | PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products |
| title_short | PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products |
| title_sort | pink1 parkin mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products |
| url | https://doi.org/10.1038/s41419-023-05595-5 |
| work_keys_str_mv | AT weili pink1parkinmediatedmitophagyinhibitsosteoblastapoptosisinducedbyadvancedoxidationproteinproducts AT wangshengjiang pink1parkinmediatedmitophagyinhibitsosteoblastapoptosisinducedbyadvancedoxidationproteinproducts AT yarusu pink1parkinmediatedmitophagyinhibitsosteoblastapoptosisinducedbyadvancedoxidationproteinproducts AT kewutu pink1parkinmediatedmitophagyinhibitsosteoblastapoptosisinducedbyadvancedoxidationproteinproducts AT linzou pink1parkinmediatedmitophagyinhibitsosteoblastapoptosisinducedbyadvancedoxidationproteinproducts AT congruiliao pink1parkinmediatedmitophagyinhibitsosteoblastapoptosisinducedbyadvancedoxidationproteinproducts AT qianwu pink1parkinmediatedmitophagyinhibitsosteoblastapoptosisinducedbyadvancedoxidationproteinproducts AT zihanwang pink1parkinmediatedmitophagyinhibitsosteoblastapoptosisinducedbyadvancedoxidationproteinproducts AT zhaomingzhong pink1parkinmediatedmitophagyinhibitsosteoblastapoptosisinducedbyadvancedoxidationproteinproducts AT jiantingchen pink1parkinmediatedmitophagyinhibitsosteoblastapoptosisinducedbyadvancedoxidationproteinproducts AT siyuanzhu pink1parkinmediatedmitophagyinhibitsosteoblastapoptosisinducedbyadvancedoxidationproteinproducts |