Table 3.

Hyaluronic acid (HA) treatment in knee OA: anti-inflammatory properties.

Reference	Intervention	Patients	Duration	Results
Nelson et al. [165]	80 mg oral preparation of HA (70%) + other GAGs versus Placebo	Oral preparation of HA + other GAGs (N = 21) Placebo (N = 19)	12 weeks	The HA-treated cohort demonstrated a notable decrease in TNFα, IL-1α, IL-1β, IL-6, IL-17α, IFN, and GM-CSF values. Furthermore, the placebo group exhibited significantly higher synovial fluid concentrations of inflammatory cytokines as well as leptin (a proinflammatory adipokine).
Wang [132]	25 mg HA + Celecoxib 200 mg/day versus 10 mg intraarticular ADA + Celecoxib 200 mg/day	HA + Celecoxib (N = 28) ADA + Celecoxib (N = 28)	4 weeks	Changes in joint stiffness did not exhibit statistically significant differences between HA + Celecoxib and ADA + Celecoxib.
Ohtori et al. [133]	25 mg HA versus 10 mg intraarticular ETN	HA (N = 20) ETN (N = 19)	4 weeks	The HA group displayed significantly weaker results in terms of joint stiffness improvement compared to ETN during the follow-up period.
Xu et al. [164]	2 mL intraarticular HA, 3 injections per knee, half-month interval 4 mL intraarticular PRP, 3 injections per knee, half-month interval 2 mL HA + 4 mL PRP, 3 injections per knee, half-month interval	HA (N = 34 knees) PRP (N = 40 knees) HA + PRP (48 knees)	24 months	The cohort that received the HA + PRP combination demonstrated IL-1β, TNFα, TIMP1, and MMP-3 inhibition at one-year posttreatment.
Raeissadat et al. [166]	3 weekly intraarticular injections of 20 mg/2 mL HA versus 3 weekly intraarticular injections of 30 μg/mL O3 (10 mL)	HA (N = 74) O3 (N = 67)	24 weeks	There was a significant reduction in joint stiffness in the group treated with HA. However, these results were not significantly different from the O3-treated cohort.