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Papers of the Week


Papers: 25 Jan 2025 - 31 Jan 2025


2025 Jan 26


Pharmacol Res


39875019

Promising LOX proteins for cartilage-targeting osteoarthritis therapy.

Authors

Morici L, Allémann E, Jordan O, Nikolic I

Abstract

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 yet approved no drugs targeting the LOX proteins. In particular, lysyl oxidase-like 2 is considered today as a new promising target for OA modifying therapy. This review clarifies the main role of different LOX proteins involved in the progression of OA. Some potential LOX inhibitor 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.