Table 1.

Biological effects of HA

Effects on extracellular matrix	Effects on immune cells	Effects on inflammatory mediators
• Enhanced HA synthesis	• Inhibits proliferation and activation	• Reduced levels of
• Enhanced synthesis of PG and chondroitin sulfate	• Reduced motility of lymphocytes and macrophages	○ Prostaglandins
		○ Leukotrienes
• Suppressed PG release from extracellular matrix	• Inhibits phagocytosis	• Increased production of cAMP
	• Suppresses aggregation of neutrophils	• Reduced expression/activity of
• Prevents PG breakdown from cartilage	• Inhibits adhesion and neutrophil-associated cartilage destruction	○ IL-1, IL-6
• Reduced markers of cartilage breakdown (chondroitin 4- and 6-sulfates)		○ Stromelysin
		○ TNF-α
		○ TIMP-1 (inhibits MMP)
		○ Plasminogen activator
		• Reduced arachidonic acid release
		• Antioxidant effects
		• Reduced production of NO

Note: Data from Moreland,¹ Abate and Salini,⁶ and Kusayama et al.⁹

Abbreviations: HA, hyaluronic acid; PG, proteoglycans; cAMP, cyclic adenosine monophosphate; IL-1, interleukin-1; IL-6, interleukin-6; TNF-α, tumor necrosis factor α; TIMP-1, tissue inhibitor of metalloproteinases-1; MMP, metalloproteinase; NO, nitric oxide.