Cartilage-protective effects of lopinavir/ritonavir: in vitro and in silico exploration of the HIF-1α/SOX9/IL-1β pathway
Abstract Background This study aimed to investigate the effects of Lopinavir/Ritonavir (Lop/r) on chondrocyte structure and extracellular matrix (ECM) integrity, as well as its impact on key proteins involved in anabolic and catabolic pathways, using both in vitro and in silico approaches. Methods D...
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BMC
2025-07-01
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| Series: | Journal of Orthopaedic Surgery and Research |
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| Online Access: | https://doi.org/10.1186/s13018-025-06068-5 |
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| author | Hanefi Ozbek Ibrahim Yilmaz Aslı Akyuz Suray Pehlivanoglu Duygu Yasar Sirin Mehmet Albayrak Omer Faruk Yilmaz |
| author_facet | Hanefi Ozbek Ibrahim Yilmaz Aslı Akyuz Suray Pehlivanoglu Duygu Yasar Sirin Mehmet Albayrak Omer Faruk Yilmaz |
| author_sort | Hanefi Ozbek |
| collection | DOAJ |
| description | Abstract Background This study aimed to investigate the effects of Lopinavir/Ritonavir (Lop/r) on chondrocyte structure and extracellular matrix (ECM) integrity, as well as its impact on key proteins involved in anabolic and catabolic pathways, using both in vitro and in silico approaches. Methods Drug-target interaction networks were constructed through bioinformatics analyses, and molecular docking was performed. Human primary chondrocytes were treated with Lop/r, and untreated cells served as controls. Cell viability, proliferation, and protein expression levels were assessed using standard in vitro techniques, including spectrophotometric assays and Western blotting. Results Molecular docking analyses revealed strong binding affinities between Lop/r and osteoarthritis-related targets such as HIF-1α, EP300, TNF, IL-6, KCNA5, and IL-1β, suggesting modulation of hypoxia, inflammatory, and epigenetic pathways. In vitro, Lop/r did not alter chondrocyte morphology or ECM structure and was not cytotoxic (p < 0.05). However, it significantly reduced the expression of critical proteins including HIF-1α, SOX9, and IL-1β (p < 0.05). Conclusion These findings suggest that Lop/r may exert regulatory effects on cartilage-related molecular pathways and holds promise as a repurposed therapeutic agent for osteoarthritis. Further studies are warranted to confirm its potential in clinical applications. |
| format | Article |
| id | doaj-art-b4df4cb54de0449a9ad86f3f0d3a72c2 |
| institution | DOAJ |
| issn | 1749-799X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj-art-b4df4cb54de0449a9ad86f3f0d3a72c22025-08-20T03:05:10ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2025-07-0120111310.1186/s13018-025-06068-5Cartilage-protective effects of lopinavir/ritonavir: in vitro and in silico exploration of the HIF-1α/SOX9/IL-1β pathwayHanefi Ozbek0Ibrahim Yilmaz1Aslı Akyuz2Suray Pehlivanoglu3Duygu Yasar Sirin4Mehmet Albayrak5Omer Faruk Yilmaz6Department of Medical Pharmacology, Usak University School of MedicineUnit of Pharmacovigilance, Republic of Turkey, Ministry of Health, Dr. Ismail Fehmi Cumalioglu City HospitalDepartment of Molecular Biology and Genetics, Faculty of Arts and Sciences, Namik Kemal UniversityDepartment of Molecular Biology and Genetics, Faculty of Arts and Sciences, Necmettin Erbakan UniversityDepartment of Molecular Biology and Genetics, Faculty of Arts and Sciences, Namik Kemal UniversityDepartment of Medical Services and Techniques, Vocational School of Health Services, Istanbul Rumeli UniversityClinics of Orthopaedic and Traumatology, Republic of Turkey, Ministry of Health, Corlu State HospitalAbstract Background This study aimed to investigate the effects of Lopinavir/Ritonavir (Lop/r) on chondrocyte structure and extracellular matrix (ECM) integrity, as well as its impact on key proteins involved in anabolic and catabolic pathways, using both in vitro and in silico approaches. Methods Drug-target interaction networks were constructed through bioinformatics analyses, and molecular docking was performed. Human primary chondrocytes were treated with Lop/r, and untreated cells served as controls. Cell viability, proliferation, and protein expression levels were assessed using standard in vitro techniques, including spectrophotometric assays and Western blotting. Results Molecular docking analyses revealed strong binding affinities between Lop/r and osteoarthritis-related targets such as HIF-1α, EP300, TNF, IL-6, KCNA5, and IL-1β, suggesting modulation of hypoxia, inflammatory, and epigenetic pathways. In vitro, Lop/r did not alter chondrocyte morphology or ECM structure and was not cytotoxic (p < 0.05). However, it significantly reduced the expression of critical proteins including HIF-1α, SOX9, and IL-1β (p < 0.05). Conclusion These findings suggest that Lop/r may exert regulatory effects on cartilage-related molecular pathways and holds promise as a repurposed therapeutic agent for osteoarthritis. Further studies are warranted to confirm its potential in clinical applications.https://doi.org/10.1186/s13018-025-06068-5ChondrocyteHIF-1αIl-1βLopinavir/ritonavirSOX9 |
| spellingShingle | Hanefi Ozbek Ibrahim Yilmaz Aslı Akyuz Suray Pehlivanoglu Duygu Yasar Sirin Mehmet Albayrak Omer Faruk Yilmaz Cartilage-protective effects of lopinavir/ritonavir: in vitro and in silico exploration of the HIF-1α/SOX9/IL-1β pathway Journal of Orthopaedic Surgery and Research Chondrocyte HIF-1α Il-1β Lopinavir/ritonavir SOX9 |
| title | Cartilage-protective effects of lopinavir/ritonavir: in vitro and in silico exploration of the HIF-1α/SOX9/IL-1β pathway |
| title_full | Cartilage-protective effects of lopinavir/ritonavir: in vitro and in silico exploration of the HIF-1α/SOX9/IL-1β pathway |
| title_fullStr | Cartilage-protective effects of lopinavir/ritonavir: in vitro and in silico exploration of the HIF-1α/SOX9/IL-1β pathway |
| title_full_unstemmed | Cartilage-protective effects of lopinavir/ritonavir: in vitro and in silico exploration of the HIF-1α/SOX9/IL-1β pathway |
| title_short | Cartilage-protective effects of lopinavir/ritonavir: in vitro and in silico exploration of the HIF-1α/SOX9/IL-1β pathway |
| title_sort | cartilage protective effects of lopinavir ritonavir in vitro and in silico exploration of the hif 1α sox9 il 1β pathway |
| topic | Chondrocyte HIF-1α Il-1β Lopinavir/ritonavir SOX9 |
| url | https://doi.org/10.1186/s13018-025-06068-5 |
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