The Role of Nutraceuticals in Osteoarthritis Prevention and Treatment: Focus on n-3 PUFAs

Table 1

Effects of PUFAs and derivatives in OA.

First author, year	References	Treatment	Properties	In vitro/in vivo models	Clinical trials
Xie et al., 2019	[1]	DHA	↓ bone mass loss; ↓ osteoclast differentiation; ↓expression of TRAP and CTSK; ↓ osteoclasts differentiation and bone remodeling; ↓ RANKL; ↓ levels of NFATc1 and MITF; ↓ angiogenesis; ↓ VEGF–VEGFR2 signaling pathway	ACLT rat OA model; RAW264.7 cells; HUVECs cells
Yu et al., 2015	[45]	LA/ALA	↓ MMP-13 and IL-1; ↓ paw swelling rate and cartilage damage	Inflammatory human chondrocytes; Sprague-Dawley rats with arthritis induced by Freund’s complete adjuvant
Wang et al., 2016	[46]	DHA	↓ MMP-13; ↓ IL-1β-induced p38 activation; ↑ thickness of articular cartilage	Human chondrosarcoma SW1353 cells; rat model of AIA
Xu et al., 2019	[48]	DHA	↓ apoptosis; ↓ activation of the MAPK signaling pathway	Human chondrosarcoma SW1353 cells
D’Adamo et al., 2020	[7]	EPA	↓ apoptosis in the presence of oxidative stress	Mouse model of OA
Phitak et al., 2018	[52]	EPA and DHA	↓ cartilage damage; ↓ ADAMTS4 secretion; ↓ NF-κB and JNK activation	Porcine cartilage explant and HACs
Kimmerling et al., 2020	[54]	n-6 PUFAs	↑ serum content of n-3 PUFAs; ↓ OA and synovitis; ↑ body weight; ↓ IFN-γ, TNF-α, and MCP-1; ↑ anti-inflammatory response	Fat-1 transgenic mouse model with PTOA induced by DMM surgery
Wu et al., 2017	[53]	HFD rich in SFA, n-3 PUFAs, or n-6 PUFAs.	↑ n-3 PUFAs, ↓ OA severity, ↑ anti-inflammatory response	Mouse model of OA induced by DMM surgery
Lu et al., 2017	[55]	Diet rich in total fat, SFAs, MUFAs, and PUFAs	↑ total fat and SFAs ↓ JSW ↑ knee OA progression; ↑ MUFAs and PUFAs ↑ JSW ↓ knee OA progression		Subjects with knee OA
Chen et al., 2018	[56]	DHA	↑ GPR120 activation; ↑ anti-inflammatory effects	GPR120 knockout mice with OA induced by ACLT; human chondrocytes	OA patients
Akbar et al., 2017	[38]	Diet supplemented with fish oil	↓ WOMAC scores; ↓ pain; ↓ use of NSAIDs/analgesic		OA patients
Sasahara et al., 2020	[59]	L-serine and EPA	↓ lumbar and knee pain		Patients with lower-back and knee pain
Lu et al., 2020	[60]	Maresin-1	↑ COL2A1; ↓ MMP-13; ↑ PI3k/Akt signaling pathway activation; ↓ NF-κB p65 signaling pathway	Rat model of OA induced by MIA; IL-1β -induced rat FLSs
Benabdoune et al., 2016	[61]	RvD1	↓ COX-2, iNOS, MMP-13; ↓ p38/MAPK, JNK 1/2, and NF-κB p65 signaling pathways; ↓ PGE2 and NO; ↓ pain; ↓ activation of caspase-3 and -9; ↓ LDH release; ↑ Bcl2 and AKT; ↑ GSH pool; ↓ oxidative stress-induced apoptosis	Human OA chondrocytes treated with IL-1β or HNE
Sun et al., 2019	[62]	RvD1	↑ macrophages’ gene expression from a proinflammatory condition to an anti-inflammatory state; ↓ cartilage degradation	Obese mice model with PTOA induced by DMM surgery

↑ increase, ↓ decrease. DHA: docosahexaenoic acid; ACLT: anterior cruciate ligament transection; OA: osteoarthritis; RAW264.7: mouse mononuclear macrophage leukemia cells; HUVECs: human umbilical vein endothelial cells; TRAP: tartrate-resistant acid phosphatase; CTSK: cathepsin K; RANKL: receptor activator of nuclear factor kappa-Β ligand; NFATc1: nuclear factor of activated T-cells, cytoplasmic 1; MITF: microphthalmia-associated transcription factor; VEGF: vascular endothelial growth factor; VEGFR2: VEGF receptor 2; LA: linoleic acid; ALA: α-linolenic acid; MMP-13: matrix metalloproteinase-13; IL-1β: interleukin-1β; AIA: adjuvant-induced arthritis; MAPK: mitogen activated protein kinase; EPA: eicosapentaenoic acid; ADAMTS4: disintegrin and metalloproteinase with thrombospondin motifs-4; NF-κB: nuclear factor-κB; JNK: c-Jun N-terminal kinases; HACs: human articular chondrocytes; n-6,-3 PUFAs: n-6,-3 polyunsaturated fatty acids; IFN-γ: interferon-γ; TNF-α: tumor necrosis factor-α; MCP-1: monocyte chemoattractant protein-1; PTOA: posttraumatic osteoarthritis; DMM: destabilization of the medial meniscus; HFD: high-fat diet; SFA: saturated fatty acids; MUFAs: monounsaturated fatty acids; JSW: joint space width; GPR120: G-protein coupled receptor 120; WOMAC: western Ontario and McMaster universities arthritis index; NSAIDs: nonsteroidal anti-inflammatory drugs; COL2A1: type II collagen; PI3K/Akt: phosphatidylinositol 3-kinase/protein kinase B; MIA: monosodium iodoacetate; FLSs: fibroblast-like synoviocytes; RvD1: resolvin D1; COX-2: cyclooxygenase-2; iNOS: inducible nitric oxide synthase; p38/MAPK: p38/mitogen activated protein kinase; NF-κB p65: nuclear factor-κB p65 subunit; PGE2: prostaglandin E2; NO: nitric oxide; HNE: 4-hydroxynonenal; LDH: lactate dehydrogenase; Bcl-2: B-cell lymphoma-2; GSH: glutathione.