Promising LOX proteins for cartilage-targeting osteoarthritis therapy
Osteoarthritis (OA) is the most affected joint disease worldwide, touching millions of people every year. It is caused by a progressive degeneration of articular cartilage, causing pain and limited mobility. Among the pathways involved in cartilage homeostasis, “LOX” proteins (referring to three dis...
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Elsevier
2025-02-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825000520 |
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| author | Luca Morici Eric Allémann Olivier Jordan Ines Nikolić |
| author_facet | Luca Morici Eric Allémann Olivier Jordan Ines Nikolić |
| author_sort | Luca Morici |
| collection | DOAJ |
| description | Osteoarthritis (OA) is the most affected joint disease worldwide, touching millions of people every year. It is caused by a progressive degeneration of articular cartilage, causing pain and limited mobility. Among the pathways involved in cartilage homeostasis, “LOX” proteins (referring to three distinct protein families, very often confused in the literature) play a prominent role. The lipoxygenase enzyme family is involved in the inflammatory process of OA by inducing the production of several pro-inflammatory leukotrienes. Lectin-like oxidized low-density lipoprotein family are receptors located at the surface of chondrocytes, which interact with their ligand, ox-LDL, activating several catabolic pathways involved in OA pathophysiology. Finally, lysyl oxidase and lysyl oxidase-like are enzymes expressed intracellularly (in chondrocytes' cytoplasm) involved in elastin biosynthesis and collagen cross-linking in cartilage extracellular matrix. EMA and FDA have not yet approved any drug targeting the LOX proteins. In particular, today lysyl oxidase-like 2 is considered as a new promising target for OA modifying therapy. This review clarifies the main roles of different LOX proteins involved in the progression of OA. Potential LOX inhibitoion strategies for drug development in advanced OA therapy, particularly for local intraarticular delivery, were listed and discussed for each target type. This review, therefore, proposes promising strategies for future drug development in OA treatment. |
| format | Article |
| id | doaj-art-84c5a90c9951481c826ecd9739bddf5b |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-84c5a90c9951481c826ecd9739bddf5b2025-02-08T04:59:55ZengElsevierPharmacological Research1096-11862025-02-01212107627Promising LOX proteins for cartilage-targeting osteoarthritis therapyLuca Morici0Eric Allémann1Olivier Jordan2Ines Nikolić3School of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, Geneva 4, 1211, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, Rue Michel-Servet 1, Geneva 4, 1211, SwitzerlandSchool of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, Geneva 4, 1211, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, Rue Michel-Servet 1, Geneva 4, 1211, SwitzerlandSchool of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, Geneva 4, 1211, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, Rue Michel-Servet 1, Geneva 4, 1211, SwitzerlandSchool of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, Geneva 4, 1211, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, Rue Michel-Servet 1, Geneva 4, 1211, Switzerland; Corresponding author at: School of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, Geneva 4, 1211, Switzerland.Osteoarthritis (OA) is the most affected joint disease worldwide, touching millions of people every year. It is caused by a progressive degeneration of articular cartilage, causing pain and limited mobility. Among the pathways involved in cartilage homeostasis, “LOX” proteins (referring to three distinct protein families, very often confused in the literature) play a prominent role. The lipoxygenase enzyme family is involved in the inflammatory process of OA by inducing the production of several pro-inflammatory leukotrienes. Lectin-like oxidized low-density lipoprotein family are receptors located at the surface of chondrocytes, which interact with their ligand, ox-LDL, activating several catabolic pathways involved in OA pathophysiology. Finally, lysyl oxidase and lysyl oxidase-like are enzymes expressed intracellularly (in chondrocytes' cytoplasm) involved in elastin biosynthesis and collagen cross-linking in cartilage extracellular matrix. EMA and FDA have not yet approved any drug targeting the LOX proteins. In particular, today lysyl oxidase-like 2 is considered as a new promising target for OA modifying therapy. This review clarifies the main roles of different LOX proteins involved in the progression of OA. Potential LOX inhibitoion strategies for drug development in advanced OA therapy, particularly for local intraarticular delivery, were listed and discussed for each target type. This review, therefore, proposes promising strategies for future drug development in OA treatment.http://www.sciencedirect.com/science/article/pii/S1043661825000520LipoxygenaseLectin-like oxidized low-density lipoprotein receptorLysyl oxidaseLysyl oxidase-likeLOXOsteoarthritis |
| spellingShingle | Luca Morici Eric Allémann Olivier Jordan Ines Nikolić Promising LOX proteins for cartilage-targeting osteoarthritis therapy Pharmacological Research Lipoxygenase Lectin-like oxidized low-density lipoprotein receptor Lysyl oxidase Lysyl oxidase-like LOX Osteoarthritis |
| title | Promising LOX proteins for cartilage-targeting osteoarthritis therapy |
| title_full | Promising LOX proteins for cartilage-targeting osteoarthritis therapy |
| title_fullStr | Promising LOX proteins for cartilage-targeting osteoarthritis therapy |
| title_full_unstemmed | Promising LOX proteins for cartilage-targeting osteoarthritis therapy |
| title_short | Promising LOX proteins for cartilage-targeting osteoarthritis therapy |
| title_sort | promising lox proteins for cartilage targeting osteoarthritis therapy |
| topic | Lipoxygenase Lectin-like oxidized low-density lipoprotein receptor Lysyl oxidase Lysyl oxidase-like LOX Osteoarthritis |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825000520 |
| work_keys_str_mv | AT lucamorici promisingloxproteinsforcartilagetargetingosteoarthritistherapy AT ericallemann promisingloxproteinsforcartilagetargetingosteoarthritistherapy AT olivierjordan promisingloxproteinsforcartilagetargetingosteoarthritistherapy AT inesnikolic promisingloxproteinsforcartilagetargetingosteoarthritistherapy |