Development of a macrophage polarization-modulating therapeutic agent for osteoarthritis treatment.

Osteoarthritis (OA) is a common chronic degenerative joint disease. Recent studies have emphasized the crucial role of macrophages, particularly tissue-resident macrophages (Tissue-Resident Macrophages, TRMs), in the pathogenesis and progression of OA. Under physiological conditions, TRMs maintain joint homeostasis, but under various stimuli, they can polarize into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. An imbalance in macrophage polarization, favoring the M1 phenotype, leads to sustained inflammation, cartilage degradation, and osteophyte formation, further exacerbating OA symptoms and structural damage. This article reviews the current understanding of macrophage polarization in OA, with a particular emphasis on the mechanisms by which TRMs influence the joint microenvironment. It explores the therapeutic potential of drug molecular platforms aimed at regulating macrophage polarization, shifting the balance from pro-inflammatory M1 to anti-inflammatory M2. The discussion includes various pharmacological agents such as corticosteroids, hyaluronic acid derivatives, monoclonal antibodies, and bioactive molecules like Squid Type II Collagen (SCII) in modulating macrophage function and slowing OA progression. Additionally, the article examines advancements in gene therapy methods targeting macrophages, utilizing nanotechnology-based delivery systems to enhance the specificity and efficiency of macrophage phenotype regulation. Targeting TRMs through sophisticated drug molecular platforms presents a promising strategy for developing novel diagnostic and therapeutic interventions for osteoarthritis.