Table 1.

Study characteristics

Author, year	Type of study (targeted/untargeted) (cross-sectional/ experimental)	Classification of biomarkers (BIPED)	Quality assessment	Metabolomic approach	Sample (cartilage, bone marrow, synovial tissue/ fluid, blood)	Number of samples
Luo et al. (Ref. 22)	Untargeted cross-sectional study C8A CD47 ANGPTL2 BSG CTSD JCAD TNC 1018 TNC 184 BGN FBLN7 THBS3 IGHM ASPN SPARC FN1 COL1A1 COL6A2	B	8	LC-MS/MS-based N-glycoproteomics analysis	Cartilage	OA + DM+ = 5 OA + DM− = 5 Control = 5
Li et al. (Ref. 23)	Targeted cross-sectional study MMP-13 ADAMTS5 GRP78 ATF6 TNF-α IL-6 NF-κB p65 GLUT-1 AGEs HIF-1α	B, P	7	Immunohistochemical staining	Synovial tissue	OA + DM+ = 10 OA + DM− = 10
Scotece et al. (Ref. 24)	Targeted cross-sectional study RBP4 Adipsin Adiponectin Leptin Resistin SF COMP MMP-1 MMP-13 Chitinase-3-like protein 1	D	8	Human ELISA-linked immunosorbent assay	Cartilage	100 OA
Silawal et al. (Ref. 25)	Targeted experimental study Collagen type I Collagen type II SOX9 Proteoglycan	P, D	6	Immunohistochemical staining	hACs	5 OA cultures
Vertti et al. (Ref. 26)	Targeted cross-sectional study SF COMP Fasting Plasma Glucose HbA1c	B	10	Human ELISA-linked immunosorbent assay	Synovial fluid	OA + DM+ = 92 OA + DM− = 29
		D			Blood	OA + DM+ = 92 OA + DM− = 29
Eitner et al. (Ref. 27)	Targeted cross-sectional study Prostaglandin E2 IL-6 C-reactive protein HbA1c Plasma triglycerides Uric acid	B, P	9	Human ELISA-linked immunosorbent assay	Synovial fluid	OA + DM+ = 23 OA + DM− = 47
					Serum	OA + DM+ = 23 OA + DM− = 47
Zhang et al. (Ref. 28)	Targeted cross-sectional study N-(Carboxymethyl)lysine N-(Carboxyethyl) lysine MG-H1 MG Plasma unsaturated phosphatidylcholines, PC ae C34:3 and PC ae C36:3	B, P	8	Mass spectrometry by flow injection analysis LC–MS/MS	Synovial fluid	OA + DM+ = 46 OA + DM− = 38
		D			Plasma	OA + DM+ = 46 OA + DM− = 38
Hamada et al. (Ref. 29)	Targeted experimental study Targeted TNF MMP-1 MMP-13 ADAMTS4 IR Akt	B, P	7	Immunohistochemistry	Synovial tissue	OA + DM+ = 7 OA + DM− = 6
		D		Immunoprecipitation and western blot analysis	Synovial tissue	OA + DM+ = 7 OA + DM− = 6
		D		qRT-PCR	Fibroblast-like-synoviocytes culture	OA + DM− = 4
Ribeiro et al. (Ref. 30)	Targeted experimental study LC3 p-rpS6 p-Akt IL-1β α-Tubulin	D	7	Western blotting	Primary human chondrocytes (HC)	OA + DM+ = 4 OA + DM− = 4 Control = 2
Zhang et al. (Ref. 31)	Untargeted cross-sectional study Plasma unsaturated phosphatidylcholines, PC ae C34:3 and PC ae C36:3	B, P	10	Ultra-high performance liquid-chromatography - mass spectrometry	Synovial fluid	OA + DM+ = 29 OA + DM− = 43 Control = 46
		D			Plasma	OA + DM+ = 29 OA + DM− = 43 DM = 25 Control = 46
Laiguillon et al. (Ref. 32)	Targeted experimental study IL-6 Prostaglandin E2	D	9	Human ELISA-linked immunosorbent assay	Homogenous isolated cartilage samples	OA + DM+ = 5 OA + DM− = 5
Tsai et al. (Ref. 33)	Targeted experimental study PKC Type I TGF receptor Type II TGF receptor Smad3 SOX9 Aggrecan Collagen type II Collagen type IX	D	6	qRT-PCR and western blot analysis	Human bone marrow-derived MSCs	3 OA
Tsai et al. (Ref. 34)	Targeted experimental study VEGF	D	7	qRT-PCR and human ELISA-linked immunosorbent assay	Human synovial fibroblast culture	35 OA
Rosa et al. (Ref. 35)	Targeted experimental study MMP-1 MMP-13 TIMP1 TIMP2 Collagen type I Collagen type II		7	qRT-PCR	Cartilage chondrocyte culture	11 OA 7 non-OA
Oren et al. (Ref. 36)	Targeted cross-sectional study Leptin Bone alkaline phosphatase Osteocalcin Pyridinium Cartilage and bone pentosidine Hydroxylysylpyridinium Lysylpyridinoline HbA1c	B, D, P	10	Human ELISA-linked immunosorbent assay	Serum	OA + DM+ = 10 OA + DM− = 10
					Synovial fluid	OA + DM+ = 10 OA + DM− = 10
				High-performance liquid chromatography	Bone and cartilage	OA + DM+ = 10 OA + DM− = 10
Rosa et al. (Ref. 37)	Targeted experimental study GLUT-1 ROS	D	7	qRT-PCR, western blot and human ELISA-linked immunosorbent assay	Cartilage chondrocyte culture	Non-OA = 15 OA = 18

ADAMTS4, a disintegrin and metalloproteinase with thrombospondin motifs 4; ADAMTS5, a disintegrin and metalloproteinase with thrombospondin motifs 5; AGEs, advanced glycation end-products; Akt, serine threonine kinase; ANGPTL2, angiopoietin-like protein 2; ASPN, asporin; ATF6, activating transcription factor 6; BGN, biglycan; BIPED, burden of disease, investigative, prognostic, efficacy of intervention and diagnostic; BSG, basigin; C8A, C8 alpha chain N437; CD47, cluster of differentiation 47; COL1A1, collagen type 1 alpha 1 chain; COL6A2, collagen type VI alpha 1 chain; CTSD, cathepsin D; FBLN7, ELISA, enzyme-linked immunosorbent assay; fibulin-7; FN1, fibronectin 1; GLUT-1, glucose transporter 1; GRP78, 78 kDa glucose-regulated protein; hAC, human articular chondrocyte; HbA1c, glycated haemoglobin; HIF-1α, hypoxia-inducible factor-1α; IGHM, immunoglobulin heavy constant mu; IL-1β, interleukin-1 beta; IL-6, interleukin-6; IR, insulin receptor; JCAD, junctional cadherin 5-associated protein; LC3, microtubule-associated protein 1A/1B-light chain 3; LC–MS/MS, liquid chromatography coupled-tandem mass spectrometry; MG, methylglyoxal; MG-H1, free methylglyoxal-derived hydroimidazolone; MMP-1, matrix metalloproteinase-1; MMP-13, matrix metalloproteinase-13; MSC, mesenchymal stem cell; NF-κB p65, RelA of nuclear factor kappa-light-chain-enhancer of activated B cells; ROS, reactive oxygen species; p-rpS6, phosphorylated ribosomal S6; qRT-PCR, quantitative real-time polymerase chain reaction; RBP4, retinol binding protein 4; SF COMP, synovial fluid cartilage oligomeric matrix protein; Smad3, SMAD family member 3; SPARC, secreted protein acidic and rich in cysteine/osteonectin; SOX9, SRY-box transcription factor 9; THBS3, thrombospondin 3; TIMP-1, tissue inhibitor of metalloproteinase-1; TIMP-2, tissue inhibitor of metalloproteinase-2; TNC, tenascin C; TNF-α, tumour necrosis factor-alpha; VEGF, vascular endothelial growth factor.

Bold biomarkers indicate significant expression change.