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Hyaluronic acid (HA) is a major extracellular matrix glycosaminoglycan that modulates inflammation and tissue regeneration via interaction with specific cell surface receptors, particularly CD44. The anti-inflammatory effect of HA is molecular weight-dependent: high molecular weight HA confers immunosuppressive and anti-inflammatory activity, while low molecular weight HA fragments can induce a pro-inflammatory response via signaling through toll-like receptors (TLR2, TLR4) and other HA-binding proteins. These receptors mediate cellular migration, cytokine release, and immune cell recruitment, playing central roles in wound healing, osteoarthritis, and other inflammatory diseases. HA is also used as a vehicle for drug delivery, targeting inflamed tissues through receptor-mediated uptake. The therapeutic manipulation of HA and its receptors represents a major avenue for modulating immune responses and promoting tissue repair.
HA binds its receptors (CD44 and others), modulating immune cell migration and cytokine production. High molecular weight HA: anti-inflammatory, immunosuppressive. Low molecular weight HA fragments: pro-inflammatory via TLR activation. HA-based drug delivery targets macrophages and inflamed tissues through receptor-mediated uptake.
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