Mechanism of hyperbaric oxygen therapy downregulating H-type angiogenesis in subchondral bone of knee osteoarthritis through the PHD2/HIF-1α pathway
Abstract Objective To explore the mechanism of hyperbaric oxygen therapy in inhibiting subchondral bone angiogenesis and delaying the progression of osteoarthritis through the PHD2/HIF-1α signaling pathway. Methods Mice were randomly divided into three groups (control group, osteoarthritis group, an...
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BMC
2025-01-01
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| Series: | Journal of Orthopaedic Surgery and Research |
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| Online Access: | https://doi.org/10.1186/s13018-025-05514-8 |
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| author | Jianjian Wang Wen Yu Yuxin Zhang Bo Chen Zhaoxiang Meng |
| author_facet | Jianjian Wang Wen Yu Yuxin Zhang Bo Chen Zhaoxiang Meng |
| author_sort | Jianjian Wang |
| collection | DOAJ |
| description | Abstract Objective To explore the mechanism of hyperbaric oxygen therapy in inhibiting subchondral bone angiogenesis and delaying the progression of osteoarthritis through the PHD2/HIF-1α signaling pathway. Methods Mice were randomly divided into three groups (control group, osteoarthritis group, and hyperbaric oxygen treatment group). The effect of hyperbaric oxygen therapy on osteoarthritis was evaluated using Micro-CT, Safranin O-Fast Green staining, and detection of osteoarthritis inflammation markers (MMP-13, ADAMTS-5, Col2a1, and Aggrecan). The activation relationship between PHD2 and downstream signaling pathways was investigated through gene knockout and overexpression experiments. Finally, cell scratch assays, tube formation assays, and chondrogenic differentiation experiments were conducted to verify the mechanism of the PHD2/HIF-1α signaling pathway under hyperbaric oxygen stimulation. Results Hyperbaric oxygen therapy delayed the progression of osteoarthritis in mice. It promoted chondrogenic differentiation of mesenchymal stem cells, inhibited angiogenesis, enhanced PHD2 expression, and suppressed the production of HIF-1α and VEGFA. Silencing/overexpression of PHD2 resulted in increased/decreased production of HIF-1α and VEGFA, respectively. Conclusion The hyperbaric oxygen environment promotes the expression of PHD2, accelerates the degradation of HIF-1α, and inhibits the production of VEGFA, thereby reducing the generation of type H vessels in subchondral bone. |
| format | Article |
| id | doaj-art-f7468cbc60a340268eed672df252ec44 |
| institution | Kabale University |
| issn | 1749-799X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj-art-f7468cbc60a340268eed672df252ec442025-01-26T12:43:21ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2025-01-0120111010.1186/s13018-025-05514-8Mechanism of hyperbaric oxygen therapy downregulating H-type angiogenesis in subchondral bone of knee osteoarthritis through the PHD2/HIF-1α pathwayJianjian Wang0Wen Yu1Yuxin Zhang2Bo Chen3Zhaoxiang Meng4Department of Rehabilitation Medicine, Northern Jiangsu People’s HospitalDepartment of Nursing, Northern Jiangsu People’s HospitalDepartment of Oral Surgery, Shanghai Ninth People’s Hospital, School of Medicine, College of Stomatology, National Center for Stomatology, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Shanghai Jiao Tong University, Shanghai Jiao Tong University, National Clinical Research Center for Oral Diseases, Shanghai Research Institute of Stomatology, Chinese Academy of Medical SciencesDepartment of Rehabilitation Medicine, Northern Jiangsu People’s HospitalDepartment of Rehabilitation Medicine, Northern Jiangsu People’s HospitalAbstract Objective To explore the mechanism of hyperbaric oxygen therapy in inhibiting subchondral bone angiogenesis and delaying the progression of osteoarthritis through the PHD2/HIF-1α signaling pathway. Methods Mice were randomly divided into three groups (control group, osteoarthritis group, and hyperbaric oxygen treatment group). The effect of hyperbaric oxygen therapy on osteoarthritis was evaluated using Micro-CT, Safranin O-Fast Green staining, and detection of osteoarthritis inflammation markers (MMP-13, ADAMTS-5, Col2a1, and Aggrecan). The activation relationship between PHD2 and downstream signaling pathways was investigated through gene knockout and overexpression experiments. Finally, cell scratch assays, tube formation assays, and chondrogenic differentiation experiments were conducted to verify the mechanism of the PHD2/HIF-1α signaling pathway under hyperbaric oxygen stimulation. Results Hyperbaric oxygen therapy delayed the progression of osteoarthritis in mice. It promoted chondrogenic differentiation of mesenchymal stem cells, inhibited angiogenesis, enhanced PHD2 expression, and suppressed the production of HIF-1α and VEGFA. Silencing/overexpression of PHD2 resulted in increased/decreased production of HIF-1α and VEGFA, respectively. Conclusion The hyperbaric oxygen environment promotes the expression of PHD2, accelerates the degradation of HIF-1α, and inhibits the production of VEGFA, thereby reducing the generation of type H vessels in subchondral bone.https://doi.org/10.1186/s13018-025-05514-8Hyperbaric oxygen therapyOsteoarthritisPHD2HIF-1αAngiogenesis |
| spellingShingle | Jianjian Wang Wen Yu Yuxin Zhang Bo Chen Zhaoxiang Meng Mechanism of hyperbaric oxygen therapy downregulating H-type angiogenesis in subchondral bone of knee osteoarthritis through the PHD2/HIF-1α pathway Journal of Orthopaedic Surgery and Research Hyperbaric oxygen therapy Osteoarthritis PHD2 HIF-1α Angiogenesis |
| title | Mechanism of hyperbaric oxygen therapy downregulating H-type angiogenesis in subchondral bone of knee osteoarthritis through the PHD2/HIF-1α pathway |
| title_full | Mechanism of hyperbaric oxygen therapy downregulating H-type angiogenesis in subchondral bone of knee osteoarthritis through the PHD2/HIF-1α pathway |
| title_fullStr | Mechanism of hyperbaric oxygen therapy downregulating H-type angiogenesis in subchondral bone of knee osteoarthritis through the PHD2/HIF-1α pathway |
| title_full_unstemmed | Mechanism of hyperbaric oxygen therapy downregulating H-type angiogenesis in subchondral bone of knee osteoarthritis through the PHD2/HIF-1α pathway |
| title_short | Mechanism of hyperbaric oxygen therapy downregulating H-type angiogenesis in subchondral bone of knee osteoarthritis through the PHD2/HIF-1α pathway |
| title_sort | mechanism of hyperbaric oxygen therapy downregulating h type angiogenesis in subchondral bone of knee osteoarthritis through the phd2 hif 1α pathway |
| topic | Hyperbaric oxygen therapy Osteoarthritis PHD2 HIF-1α Angiogenesis |
| url | https://doi.org/10.1186/s13018-025-05514-8 |
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