Introduction
Materials and methods
Control individuals
Patients with early osteoarthritis
Patients with late osteoarthritis
Power analysis
Reduction/alkylation of synovial fluid samples and electropheresis
Mass spectrometry
Processing of mass spectrometry data
Principal component analysis
Wilcoxon's rank sum test
Results
Synovial fluid protein profiles
GI# | Protein |
---|---|
21493031 | A kinase (PRKA) anchor protein 13 |
4501885 | Actin, beta |
4501887 | Actin, gamma 1 |
4501889 | Actin, gamma 2, smooth muscle, enteric |
4501987 | Afamin |
6995994 | Aggrecan 1 (chondroitin sulfate proteoglycan 1, large aggregating proteoglycan, antigen identified by monoclonal antibody A0122) |
4502027 | Albumin |
55743106 | Alpha 3 type VI collagen isoform 5 precursor (NP_476508) |
21071030 | Alpha-1-B glycoprotein |
4502067 | Alpha-1-microglobulin/bikunin precursor |
4502337 | Alpha-2-glycoprotein 1, zinc |
4502005 | Alpha-2-HS-glycoprotein |
4557225 | Alpha-2-macroglobulin |
40254482 | Amylase, alpha 1A; salivary |
4502133 | Amyloid P component, serum |
4557287 | Angiotensinogen (serine [or cysteine] proteinase inhibitor, clade A [alpha-1 antiproteinase, antitrypsin], member 8) |
4502149 | Apolipoprotein A-II |
4502151 | Apolipoprotein A-IV |
4502153 | Apolipoprotein B (including Ag [x] antigen) |
4502157 | Apolipoprotein C-I |
32130518 | Apolipoprotein C-II |
4502163 | Apolipoprotein D |
4557325 | Apolipoprotein E |
4557327 | Apolipoprotein H (beta-2-glycoprotein I) |
4502397 | B-factor, properdin |
4757826 | Beta-2-microglobulin |
57634528 | Carboxypeptidase N, polypeptide 2, 83 kD (NP_001300 removed for review) |
47777317 | Cartilage acidic protein 1 |
51944962 | Cartilage intermediate layer protein (NP_003604) |
40217843 | Cartilage oligomeric matrix protein |
4557485 | Ceruloplasmin (ferroxidase) |
42716297 | Clusterin (complement lysis inhibitor, SP-40,40, sulfated glycoprotein 2, testosterone-repressed prostate message 2, apolipoprotein J) |
42740907 | Clusterin (complement lysis inhibitor, SP-40,40, sulfated glycoprotein 2, testosterone-repressed prostate message 2, apolipoprotein J) |
4503635 | Coagulation factor II (thrombin) |
15011913 | Collagen, type VI, alpha 1 |
7705753 | Complement component 1, q subcomponent, alpha polypeptide |
11038662 | Complement component 1, q subcomponent, beta polypeptide |
56786155 | Complement component 1, q subcomponent, gamma polypeptide (NP_758957) |
4502493 | complement component 1, r subcomponent |
41393602 | Complement component 1, s subcomponent |
14550407 | Complement component 2 |
4557385 | Complement component 3 |
4502501 | Complement component 4A |
14577919 | Complement component 4A |
50345296 | Complement component 4B preproprotein (NP_001002029) |
38016947 | Complement component 5 |
4559406 | Complement component 6 |
45580688 | Complement component 7 |
4557393 | Complement component 8, gamma polypeptide |
54792787 | Complement factor H-related 3 (NP_066303) |
4885165 | Cystatin A (stefin A) |
4503107 | Cystatin SA |
42544239 | D component of complement (adipsin) |
16751921 | Dermcidin |
58530842 | Desmoplakin isoform II (NP_001008844) |
11761629 | Fibrinogen, alpha chain isoform alpha preproprotein |
4503689 | Fibrinogen, alpha chain isoform alpha-E preproprotein |
11761631 | Fibrinogen, B beta polypeptide |
4503715 | Fibrinogen, gamma chain isoform gamma-A precursor |
11761633 | Fibrinogen, gamma chain isoform gamma-B precursor |
47132557 | Fibronectin 1 isoform 1 preproprotein |
47132551 | Fibronectin 1 isoform 2 preproprotein |
16933542 | Fibronectin 1 isoform 3 preproprotein |
47132555 | Fibronectin 1 isoform 4 preproprotein |
47132553 | Fibronectin 1 isoform 5 preproprotein |
47132549 | Fibronectin 1 isoform 6 preproprotein |
4504165 | Gelsolin (amyloidosis, Finnish type) |
6006001 | Glutathione peroxidase 3 (plasma) |
32483410 | Group-specific component (vitamin D binding protein) |
4504375 | H factor 1 (complement) |
4826762 | Haptoglobin |
45580723 | Haptoglobin-related protein |
4504345 | Hemoglobin, alpha 1 |
4504349 | Hemoglobin, beta |
4504351 | Hemoglobin, delta |
11321561 | Hemopexin |
4504489 | Histidine-rich glycoprotein |
4504579 | I factor (complement) |
21489959 | Immunoglobulin J polypeptide, linker protein for immunoglobulin alpha and mu polypeptides |
13399298 | Immunoglobulin lambda-like polypeptide 1 |
4826772 | Insulin-like growth factor binding protein, acid labile subunit |
4504781 | Inter-alpha (globulin) inhibitor H1 |
4504783 | Inter-alpha (globulin) inhibitor H2 |
31542984 | Inter-alpha (globulin) inhibitor H4 (plasma Kallikrein-sensitive glycoprotein) |
4504893 | Kininogen 1 |
54607120 | Lactotransferrin (NP_002334) |
4504985 | Lectin, galactoside-binding, soluble, 7 (galectin 7) |
5031885 | Lipoprotein, Lp(a) |
4505047 | Lumican |
9257232 | Orosomucoid 1 |
4505529 | Orosomucoid 2 |
19923106 | Oaraoxonase 1 |
4505881 | Plasminogen |
51476111 | PREDICTED: similar to Apolipoprotein A-I precursor (Apo-AI) (XP_496536) |
51476113 | PREDICTED: similar to Apolipoprotein C-III precursor (Apo-CIII) (XP_496537) |
51472914 | PREDICTED: similar to KIAA1501 protein (XP_370973) |
4506355 | Pregnancy-zone protein |
4505821 | Prolactin-induced protein |
4506117 | Protein S (alpha) |
5031925 | Proteoglycan 4, (megakaryocyte stimulating factor, articular superficial zone protein, camptodactyly, arthropathy, coxa vara, pericarditis syndrome) |
55743122 | Retinol-binding protein 4, plasma precursor (NP_006735) |
4506773 | S100 calcium binding protein A9 (calgranulin B) |
50363217 | Serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1 (NP_000286) |
50363221 | Serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1 (NP_001002235) |
50363219 | Serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1 (NP_001002236) |
4502595 | Serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6 |
50659080 | Serine (or cysteine) proteinase inhibitor, clade A, member 3 precursor (NP_001076) |
4502261 | Serine (or cysteine) proteinase inhibitor, clade C (antithrombin), member 1 |
39725934 | Serine (or cysteine) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1 |
4557379 | Serine (or cysteine) proteinase inhibitor, clade G (C1 inhibitor), member 1 (angioedema, hereditary) |
10835095 | Serum amyloid A4, constitutive |
41150478 | Similar to immunoglobulin M chain |
4507557 | Tetranectin (plasminogen binding protein) |
4557871 | Transferrin |
4507725 | Transthyretin (prealbumin, amyloidosis type I) |
4507895 | Vimentin |
18201911 | Vitronectin (serum spreading factor, somatomedin B, complement S-protein) |
Unsupervised principal component analysis of protein profiles
Differentially abundant proteins in healthy versus osteoarthritis proteomic profiles
GI# | Protein description | Upregulated in | Specificity | Sensitivity | P value (Fisher's exact, two sided) |
---|---|---|---|---|---|
4885165 | Cystatin A (stefin A) | Control | 0.650 | 1.000 | 1.92 × e-08 |
6995994 | Aggrecan 1 (chondroitin sulfate proteoglycan 1) | Control | 0.650 | 0.974 | 2.30 × e-07 |
1651921 | Dermcidin | Control | 0.600 | 1.000 | 1.13 × e-07 |
4502027 | Albumin | OA | 0.950 | 0.718 | 7.96 × e-07 |
4502067 | α1-Microglobulin/bikunin precursor | OA | 0.950 | 0.718 | 7.96 × e-07 |
4503689 | Fibrinogen, α chain isoform α-E preprotein | OA | 0.950 | 0.718 | 7.96 × e-07 |
4503715 | Fibrinogen, γ chain isoform γ-A precursor | OA | 1.000 | 0.744 | 1.43 × e-08 |
4557225 | α2-Macroglobulin | OA | 0.950 | 0.718 | 7.96 × e-07 |
4557325 | Apolipoprotein E | OA | 1.000 | 0.744 | 1.43 × e-08 |
4557327 | Apolipoprotein H (β2-glycoprotein I) | OA | 1.000 | 0.744 | 1.43 × e-08 |
4557385 | Complement component 3 (gel slice 3) | OA | 0.950 | 0.718 | 7.96 × e-07 |
4557385 | Complement component 3 (gel slice 5) | OA | 1.000 | 0.744 | 1.43 × e-08 |
4557485 | Ceruloplasmin (ferroxidase) | OA | 0.950 | 0.718 | 7.96 × e-07 |
4826762 | Haptoglobin | OA | 0.950 | 0.718 | 7.96 × e-07 |
9257232 | Orosomucoid 1 | OA | 0.850 | 0.667 | 2.51 × e-04 |
32483410 | Group specific component (vitamin D binding protein) | OA | 1.000 | 0.744 | 1.43 × e-08 |
50345296 | Complement component 4B preprotein (NP_001002029) | OA | 1.000 | 0.744 | 1.43 × e-08 |
5147611 | PREDICTED: similar to apolipoprotein A-1 precursor (apo-A-1; XP_496536) | OA | 0.950 | 0.718 | 7.96 × e-07 |
55743122 | Retinol-binding protein 4, plasma precursor (NP_006735) | OA | 0.900 | 0.692 | 1.87 × e-05 |
Differentially abundant proteins in discrete osteoarthritis subsets
Abundant synovial fluid proteins as potential biomarkers
Discussion
Serine protease inhibitors | Cartilage metabolism | Collagen metabolism cytoskeletal proteins | Inflammation | Immunologic cascade | Oxidative stress | Apoptosis |
---|---|---|---|---|---|---|
AT III | Fibronectin | Collagen V1 | Fibrinogen | CLIP | Aflamin | Fibrinogen |
C1 inhibitor | IGFBP | α1-Antitrypsin | Kinninogen | Complement C3/C4/C6/C8 | Paraoxonase | Vimentin |
PEDF | Clustrin | Tetranectin | Clusterin | Factor H and factor I | α1-Proteinase inhibitor | Apolipoprotein A |
α1-Antitrypsin | PEDF | Fibronectin | Tetranectin | Fibronectin | Clustrin | H4 inhibitor |
α1-Antichymotrypsin | Pregnancy zone protein | Gelsolin | α1-Acid glycoprotein | Fibrinogen | S100 | |
Kinninogen | Albumin | SHAP | S100 | Immuglobulin J polypeptide | ||
Pregnancy zone protein | CILP | Lumican | PEDF | |||
C1q (with C1s and C1r) | Cartilage acidic protein | Vimentin | Apolipoprotein A/E | |||
COMP | Complement C3/C4/C6/C8 | |||||
Factors H and I | ||||||
Carboxypeptidase |