<i>Prg4</i> and Osteoarthritis: Functions, Regulatory Factors, and Treatment Strategies

Proteoglycan 4 (PRG4), also known as lubricin, plays a critical role in maintaining joint homeostasis by reducing friction between articular cartilage surfaces and preventing cartilage degradation. Its deficiency leads to early-onset osteoarthritis (OA), while overexpression can protect against cart...

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Main Authors: Peng-Jie Fu, Sheng-Yuan Zheng, Yan Luo, Zhuo-Qun Ren, Zi-Han Li, Ya-Ping Wang, Bang-Bao Lu
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/3/693
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Summary:Proteoglycan 4 (PRG4), also known as lubricin, plays a critical role in maintaining joint homeostasis by reducing friction between articular cartilage surfaces and preventing cartilage degradation. Its deficiency leads to early-onset osteoarthritis (OA), while overexpression can protect against cartilage degeneration. Beyond its lubricating properties, PRG4 exerts anti-inflammatory effects by interacting with Toll-like receptors, modulating inflammatory responses within the joint. The expression of <i>Prg4</i> is regulated by various factors, including mechanical stimuli, inflammatory cytokines, transcription factors such as Creb5 and FoxO, and signaling pathways like TGF-β, EGFR, and Wnt/β-catenin. Therapeutic strategies targeting <i>PRG4</i> in OA have shown promising results, including recombinant PRG4 protein injections, gene therapies, and small molecules that enhance endogenous <i>Prg4</i> expression or mimic its function. Further research into the molecular mechanisms regulating <i>Prg4</i> expression will be essential in developing more effective OA treatments. Understanding the interplay between <i>Prg4</i> and other signaling pathways could reveal novel therapeutic targets. Additionally, advancements in gene therapy and biomaterials designed to deliver PRG4 in a controlled manner may hold potential for the long-term management of OA, improving patient outcomes and delaying disease progression.
ISSN:2227-9059