Table 4.

Effect of PUFAs on osteoarthritis from cellular and animal experiments.

Study Type	PUFAs Type	Subject	Dose	Effects	Mechanisms	Ref.
In vitro	DHA	Human osteoarthritis chondrocyte	50 μg/mL for 1 h	Promoted chondrocyte proliferation Suppressed apoptosis and elevated autophagy	↑ Beclin-1 and Bcl-2 ↓ p-JNK, p-p38, p-mTOR, and LC3-I/II ratio	[129]
In vivo	DHA	SD rats	5 g/kg for 6 weeks, supplemented in diet		↑ Collagen II–positive cell rate ↓ Mankin score	[129]
In vitro	DHA	SW1353 cells	10 μM for 24 h	Alleviated osteoarthritis progression	↑ SIRT1 ↓ HMGB1, RAGE, TLR4, and Caspase-8	[130]
In vivo	Fish oil	Obesity-related post-traumatic osteoarthritis mice	8.4% w/w for 14 weeks, supplemented in diet			[130]
In vitro	n-3/n-6 PUFAs	SW1353 cells	NA	n-6 PUFAs exacerbated obesity-related osteoarthritis n-3 PUFAs were protective	n-6: ↑ TLR4, NF-κB, and NLRP3 n-3: ↓ TLR4, NF-κB, and NLRP3	[131]
In vivo	n-3/n-6 PUFAs	Obesity-related post-traumatic osteoarthritis mice				[131]
In vitro	DHA	RAW264.7 cells	NA	Protected cartilage by inhibiting the ability of bone remodeling and angiogenesis	↓ CTSK, TRAP, NFATc1, MITF, VEGF-C, VEGF-A, and VEGFR2	[132]
In vivo	DHA	ACLT-induced rats	1 mg/kg every other day for 2 months, injected in tail		↓ RANKL, CD31, and endomucin	[132]

Abbreviations: ACLT—anterior cruciate ligament transection; Bcl-2—B-cell lymphoma-2; CTSK—cathepsin K; DHA—docosahexaenoic acid; HMGB1—high-mobility group box 1; JNK—c-Jun N-terminal kinase; LC3—light chain 3; MITF—microphthalmia transcription factor; mTOR—mammalian target of rapamycin; NA—not available; NF-κB—nuclear factor-κ-gene binding; NFATc1—nuclear factor of activated T-cells cytoplasmic 1; NLRP3—NOD-like receptor protein 3; PUFA—polyunsaturated fatty acid; RAGE—receptor for advanced glycation end products; RANKL—receptor activator of nuclear factor κB ligand; SD rat—Sprague Dawley rat; SIRT1—sirtuin 1; TLR4—toll-like receptor 4; TRAP—tartrate-resistant acid phosphatase; VEGF—vascular endothelial growth factor; VEGFR—vascular endothelial growth factor receptor; ↑—up regulation; ↓—down regulation.