Denosumab ameliorates osteoarthritis by protecting cartilage against degradation and modulating subchondral bone remodeling
Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. Effective management for early-stage OA is crucial. Denosumab (DS) has been widely used to treat osteoporosis (OP) and rheumatoid arthritis, but its potential for managing OA remains clear. We assessed the effects of DS...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Regenerative Therapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320424000518 |
| _version_ | 1797237973699264512 |
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| author | Lei Shangguan Ming Ding Yingchun Wang Hu Xu Binghui Liao |
| author_facet | Lei Shangguan Ming Ding Yingchun Wang Hu Xu Binghui Liao |
| author_sort | Lei Shangguan |
| collection | DOAJ |
| description | Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. Effective management for early-stage OA is crucial. Denosumab (DS) has been widely used to treat osteoporosis (OP) and rheumatoid arthritis, but its potential for managing OA remains clear. We assessed the effects of DS on osteoclast activity and chondrocyte apoptosis using tartrate-resistant acid phosphatase (TRAP) assay, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, and TUNEL staining. To assess the impact of DS on the NF-κB pathway, we performed Western blot and immunofluorescence staining. Additionally, we used an OA model to explore the influence of DS on subchondral bone remodeling and cartilage degeneration in vivo. We found that DS hindered receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis by inhibiting the activity of the NF-κB pathway. Besides, DS alleviated reactive oxygen species (ROS)-induced apoptosis in chondrocytes by regulating the expression of genes related to apoptosis. Moreover, we observed an attenuation of OA-related subchondral bone remodeling and cartilage degeneration in vivo. Our findings indicate that DS could effectively suppress osteoclast activity and chondrocyte apoptosis, thereby mitigating OA-related subchondral bone remodeling and cartilage degeneration. These results provide a mechanistic basis for using DS to treat OA. |
| first_indexed | 2024-04-24T17:28:15Z |
| format | Article |
| id | doaj.art-7c1026a570b44c0b8c345c40b10be90d |
| institution | Directory Open Access Journal |
| issn | 2352-3204 |
| language | English |
| last_indexed | 2024-04-24T17:28:15Z |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj.art-7c1026a570b44c0b8c345c40b10be90d2024-03-28T06:38:06ZengElsevierRegenerative Therapy2352-32042024-12-0127181190Denosumab ameliorates osteoarthritis by protecting cartilage against degradation and modulating subchondral bone remodelingLei Shangguan0Ming Ding1Yingchun Wang2Hu Xu3Binghui Liao4Department of Orthopedic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, ChinaDepartment of Orthopedic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, ChinaDepartment of Orthopedic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, ChinaDepartment of Orthopedic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, ChinaCorresponding author.; Department of Orthopedic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, ChinaOsteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. Effective management for early-stage OA is crucial. Denosumab (DS) has been widely used to treat osteoporosis (OP) and rheumatoid arthritis, but its potential for managing OA remains clear. We assessed the effects of DS on osteoclast activity and chondrocyte apoptosis using tartrate-resistant acid phosphatase (TRAP) assay, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, and TUNEL staining. To assess the impact of DS on the NF-κB pathway, we performed Western blot and immunofluorescence staining. Additionally, we used an OA model to explore the influence of DS on subchondral bone remodeling and cartilage degeneration in vivo. We found that DS hindered receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis by inhibiting the activity of the NF-κB pathway. Besides, DS alleviated reactive oxygen species (ROS)-induced apoptosis in chondrocytes by regulating the expression of genes related to apoptosis. Moreover, we observed an attenuation of OA-related subchondral bone remodeling and cartilage degeneration in vivo. Our findings indicate that DS could effectively suppress osteoclast activity and chondrocyte apoptosis, thereby mitigating OA-related subchondral bone remodeling and cartilage degeneration. These results provide a mechanistic basis for using DS to treat OA.http://www.sciencedirect.com/science/article/pii/S2352320424000518OsteoarthritisDenosumabOsteoclastChondrocyte |
| spellingShingle | Lei Shangguan Ming Ding Yingchun Wang Hu Xu Binghui Liao Denosumab ameliorates osteoarthritis by protecting cartilage against degradation and modulating subchondral bone remodeling Regenerative Therapy Osteoarthritis Denosumab Osteoclast Chondrocyte |
| title | Denosumab ameliorates osteoarthritis by protecting cartilage against degradation and modulating subchondral bone remodeling |
| title_full | Denosumab ameliorates osteoarthritis by protecting cartilage against degradation and modulating subchondral bone remodeling |
| title_fullStr | Denosumab ameliorates osteoarthritis by protecting cartilage against degradation and modulating subchondral bone remodeling |
| title_full_unstemmed | Denosumab ameliorates osteoarthritis by protecting cartilage against degradation and modulating subchondral bone remodeling |
| title_short | Denosumab ameliorates osteoarthritis by protecting cartilage against degradation and modulating subchondral bone remodeling |
| title_sort | denosumab ameliorates osteoarthritis by protecting cartilage against degradation and modulating subchondral bone remodeling |
| topic | Osteoarthritis Denosumab Osteoclast Chondrocyte |
| url | http://www.sciencedirect.com/science/article/pii/S2352320424000518 |
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