Introduction
Materials and methods
Human bone samples
RNA extraction
Microarray
Sample pair | |||||||
---|---|---|---|---|---|---|---|
Slide | GEO accession number | ID | Status | Age (years) | ID | Status | Age (years) |
1 | GSM207548 | 1 | CTL | 85 | 12 | OA | 83 |
2 | GSM207549 | 2 | CTL | 83 | 13 | OA | 82 |
3 | GSM207810 | 2 | CTL | 83 | 14 | OA | 82 |
4 | GSM207811 | 3 | CTL | 72 | 15 | OA | 78 |
5 | GSM207550 | 4 | CTL | 72 | 16 | OA | 77 |
6 | GSM207812 | 5 | CTL | 68 | 21 | OA | 68 |
7 | GSM207552 | 6 | CTL | 68 | 17 | OA | 66 |
8 | GSM207553 | 7 | CTL | 60 | 18 | OA | 60 |
9 | GSM207554 | 8 | CTL | 56 | 19 | OA | 56 |
10 | GSM207555 | 9 | CTL | 43 | 20 | OA | 49 |
11 | GSM208577 | 37 | CTL | 85 | 47 | OA | 85 |
12 | GSM208575 | 38 | CTL | 73 | 48 | OA | 77 |
13 | GSM208578 | 39 | CTL | 71 | 49 | OA | 73 |
14 | GSM208576 | 40 | CTL | 71 | 50 | OA | 70 |
15 | GSM208579 | 41 | CTL | 70 | 51 | OA | 69 |
16 | GSM208583 | 42 | CTL | 69 | 52 | OA | 63 |
17 | GSM208580 | 43 | CTL | 64 | 53 | OA | 63 |
18 | GSM208582 | 44 | CTL | 60 | 54 | OA | 62 |
19 | GSM208581 | 45 | CTL | 57 | 55 | OA | 57 |
20 | GSM208584 | 46 | CTL | 50 | 56 | OA | 50 |
21 | GSM207805 | 26 | OP | 91 | 22 | OA | 87 |
22 | GSM207813 | 27 | OP | 87 | 12 | OA | 83 |
23 | GSM207803 | 34 | OP | 87 | 13 | OA | 82 |
24 | GSM207804 | 28 | OP | 84 | 23 | OA | 79 |
25 | GSM207808 | 29 | OP | 81 | 24 | OA | 78 |
26 | GSM207806 | 35 | OP | 78 | 15 | OA | 78 |
27 | GSM207807 | 36 | OP | 78 | 16 | OA | 77 |
28 | GSM207556 | 35 | OP | 78 | 25 | OA | 73 |
29 | GSM208574 | 32 | OP | 74 | 21 | OA | 68 |
30 | GSM207809 | 33 | OP | 74 | 17 | OA | 66 |
32 | GSM207798 | 2 | CTL | 83 | 27 | OP | 87 |
33 | GSM207557 | 2 | CTL | 83 | 34 | OP | 87 |
34 | GSM207796 | 10 | CTL | 83 | 28 | OP | 84 |
35 | GSM207797 | 11 | CTL | 74 | 29 | OP | 81 |
36 | GSM207799 | 4 | CTL | 72 | 36 | OP | 78 |
37 | GSM207800 | 3 | CTL | 72 | 30 | OP | 77 |
38 | GSM207551 | 3 | CTL | 72 | 31 | OP | 75 |
39 | GSM207801 | 5 | CTL | 68 | 32 | OP | 74 |
40 | GSM207802 | 6 | CTL | 68 | 33 | OP | 74 |
Real-time PCR
Gene/primer (GenBank accession number) | Forward | Reverse |
---|---|---|
GAPDH (NM_002046) | ACCCAGAAGACTGTGGATGG | CAGTGAGCTTCCCGTTCAG |
ADAMTS4 (NM_005099) | GGCTACTACTATGTGCTGGAGC | TCCGCACACCATGCACTTGTCA |
ADM (NM_001124) | GGATGAAGCTGGTTTCCGTC | GACTCAGAGCCCACTTATTC |
ADFP (NM_001122) | GTTGCCAATACCTATGCCTG | CAGTAGTCGTCACAGCATCT |
CD14 (NM_000591) | GAGGTTCGGAAGACTTATCG | ATCTTCATCGTCCAGCTCAC |
COL4A1 (NM_001845) | TAGAGAGGAGCGAGATGTTC | GTGACATTAGCTGAGTCAGG |
CTNNB1 (NM_001904) | GGTGCTATCTGTCTGCTCTAGT | GACGTTGACTTGGATCTGTCAGG |
FST (NM_006350) | GGCAAGATGTAAAGAGCAGC | CATTATTGGTCTGGTCCACC |
GADD45B (NM_015675) | TTGCAACATGACGCTGGAAG | CATTCATCAACTTGGCCGAC |
IBSP (NM_004967) | CAATCCAGCTTCCCAAGAAG | CTTCTGCTTCGCTTTCTTCG |
INHBA (NM_002192) | GAACTTATGGAGCAGACCTC | TGCCTTCCTTGGAAATCTCG |
INSIG1 (NM_005542) | TGTATCGACAGTCACCTCGGA | GGACAGCTGGACATTATTGGC |
ITGB2 (NM_000211)) | AAGTGACGCTTTACCTGCGA | CCTGAGGTCATCAAGCATGG |
KLF6 (NM_001300) | TGTGCAGCATCTTCCAGGAG | AACGTTCCAGCTCTAGGCAG |
MEPE (NM_020203) | GCAAAGCTGTGTGGAAGAGCAGA | CCCTTATTCTCACTGGCTTCAG |
MMP25 (NM_004142) | ATGTCACCGTCAGCAACGCA | CGGTCTTGATGCTGTTCTTG |
MT2A (NM_005953) | GCAAATGCACCTCCTGCAAG | GTGGAAGTCGCGTTCTTTAC |
NHERF1 (NM_004252) | TCACCAATGGGGAGATACAG | GTCTTGGGAATTCAGCTCCT |
PTEN (NM_000314) | AAGACAAAGCCAACCGATAC | GAAGTTGAACTGCTAGCCTC |
RUNX2 (NM_004348) | TGATGACACTGCCACCTCTG | GGGATGAAATGCTTGGGAAC |
S100A4 (NM_002961) | GTCAGAACTAAAGGAGCTGC | TGTTGCTGTCCAAGTTGCTC |
SMAD3 (NM_005902) | TTCAACAACCAGGAGTTCGC | TACTGGTCACAGTA |
STC1 (NM_003155) | CCTGTGACACAGATGGGATG | GAATGGCGAGGAAGACCTTG |
TIMP4 (NM_003256) | TTGACTGGTCAGGTCCTCAGT | GGTACTGTGTAGCAGGTGGT |
TWIST1 (NM_000474) | TCAGCAGGGCCGGAGACCTAGAT | GTCTGGGAATCACTGTCCAC |
WNT5B (AY009399) | ACCCTACTCTGGAAACTGTC | TAAACATCTCGGGTCTCTGC |
Statistical analysis
Results
Microarray analysis of OA, control and OP bone samples
Identification and functional classification of top-ranking differentially expressed genes in OA bone
Real-time PCR | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Rank | GenBank | Role | Cell type | Pathway | Symbol | Name | t OA/CTL | t OA/OP | Symbol | OA/CTL |
ADAMTS4
| 0.11 | |||||||||
2 | NM_001124 | A, B, C | OB, OC, OS, CB | TGF-β/BMP |
ADM
| Adrenomedullin | -12.620 | -7.904 |
ADM
| 0.09 |
3 | NM_002450 | B | OB |
MT1L
| Metallothionein 1L | -8.342 | -6.843 | |||
4 | NM_016109 | A | WNT |
ANGPTL4
| Angiopoietin-like 4 | -6.165 | -8.052 | |||
5 | NM_015675 | B | OB, OC, CB | TGF-β/BMP |
GADD45B
| Growth arrest and DNA-damage-inducible, beta | -8.102 | -5.985 |
GADD45B
| 0.15 |
7 | NM_000358 | A, B | TGF-β/BMP |
TGF-BI
| Transforming growth factor, beta-induced | -6.915 | -5.741 | |||
9 | NM_017817 |
RAB20
| RAB20, member RAS oncogene family | -5.147 | -6.982 | |||||
10 | NM_004967 | B, C | OB, CB | WNT & TGF-β/BMP |
IBSP
| Integrin-binding sialoprotein | -5.088 | -5.865 |
IBSP
| 0.25 |
12 | AB014526 | B | OB |
MFAP3L
| Microfibrillar-associated protein 3-like | 5.284 | 4.983 | |||
13 | NM_004142 | A, B, C | OB, OC, CB | WNT |
MMP25
| Matrix metalloproteinase 25 | 4.942 | 7.183 |
MMP25
| 2.60 |
15 | NM_002025 | B | TGF-β/BMP |
FMR2
| Fragile × mental retardation 2 | 4.915 | 4.851 | |||
18 | NM_005953 | B | OB |
MT2A
| Metallothionein 2A | -4.638 | -7.071 |
MT2A
| 0.18 | |
20 | NM_013258 | A, B | M OC |
PYCARD
| PYD and CARD domain containing | 6.567 | 4.355 | |||
21 | NM_014467 |
SRPX2
| Sushi-repeat-containing protein, X-linked 2 | -4.333 | -4.918 | |||||
22 | NM_003155 | A, B, C | OB, OC, CB |
STC1
| Stanniocalcin 1 | -6.656 | -4.274 |
STC1
| 0.16 | |
23 | NM_001109 | B | OC |
ADAM8
| A disintegrin and metalloproteinase domain 8 | 5.426 | 4.269 | |||
24 | NM_020203 | B | OB, OS | TGF-β/BMP |
MEPE
| Matrix, extracellular phosphoglycoprotein with ASARM motif | -5.036 | -4.263 |
MEPE
| 0.11 |
28 | S68954 | B | OB |
MT1G
| Metallothionein 1G | -4.202 | -7.630 | |||
29 | AK026438 | B | OB |
GALNT4
| Polypeptide N-acetylgalactosaminyltransferase 4 | 5.259 | 4.195 | |||
30 | NM_000474 | B | OB | WNT |
TWIST1
| Twist homolog 1 | -4.194 | -4.910 |
TWIST1
| 0.31 |
33 | NM_000655 | B | M |
SELL
| Selectin L | 4.852 | 4.179 | |||
36 | NM_002341 | A, B, C | OB, CB |
LTB
| Lymphotoxin beta | 4.465 | 4.086 | |||
37 | NM_003226 | A |
TFF3
| Trefoil factor 3 | 4.080 | 4.074 | ||||
42 | NM_000607 | B | M |
ORM1
| Orosomucoid 1 | 4.284 | 3.982 | |||
46 | NM_005542 |
INSIG1
| Insulin induced gene 1 | -7.756 | -3.878 |
INSIG1
| 0.55 | |||
49 | NM_001302 | B | M |
CORT
| Cortistatin | -6.713 | -3.843 | |||
52 | NM_000598 | A, B, C | OB, OC, CB | WNT & TGF-β/BMP |
IGFBP3
| Insulin-like growth factor binding protein 3 | -3.772 | -3.893 | ||
54 | NM_012479 | A, B | OB |
YWHAG
| Tyrosine 3-/tryptophan 5-monooxygenase activation protein, gamma | -3.759 | -5.355 | |||
59 | NM_014624 | B | OB | WNT |
S100A6
| S100 calcium binding protein A6 | 8.214 | 3.710 | ||
61 | NM_006732 | A, B | OB |
FOSB
| FBJ murine osteosarcoma viral oncogene homolog B | 3.682 | 3.926 | |||
64 | NM_002961 | A, B | OB | WNT |
S100A4
| S100 calcium binding protein A4 | 4.407 | 3.596 |
S100A4
| 2.43 |
65 | NM_016184 | B | M |
CLECSF6
| C-type lectin domain family 4, member A | 4.575 | 3.594 | |||
68 | NM_006184 | B |
NUCB1
| Nucleobindin 1 | -3.551 | -5.513 | ||||
69 | NM_001300 | A | WNT & TGF-β/BMP |
KLF6
| Kruppel-like factor 6 | -4.047 | -3.544 |
KLF6
| 0.41 | |
70 | NM_004864 | A, B | OB, CB | TGF-β/BMP |
GDF15
| Growth differentiation factor 15 | -3.541 | -4.269 | ||
73 | U79271 | B | OB, OC | WNT |
AKT3
| V-akt murine thymoma viral oncogene homolog 3 | 3.507 | 4.876 | ||
76 | S83282 | A, B | OB, OC |
MIF
| Macrophage migration inhibitory factor | -3.654 | -3.496 | |||
81 | NM_005213 | B | OC |
CSTA
| Cystatin A | 4.450 | 3.447 | |||
82 | NM_000647 | A, B | M OC |
CCR2
| Chemokine (C-C motif) receptor 2 | 7.277 | 3.446 | |||
85 | NM_001911 | A |
CTSG
| Cathepsin G | 8.474 | 3.411 | ||||
87 | NM_001122 | WNT |
ADFP
| Adipose differentiation-related protein | -3.368 | -10.219 |
ADFP
| 0.21 | ||
92 | NM_006254 | A, B | OB |
PRKCD
| Protein kinase C, delta | 5.549 | 3.319 | |||
94 | NM_002162 | A |
ICAM3
| Intercellular adhesion molecule 3 | 3.304 | 5.798 | ||||
95 | NM_001885 | B | OB, OC |
CRYAB
| Crystallin, alpha B | -3.296 | -7.616 | |||
96 | D17152 | A | WNT |
SOD2
| superoxide dismutase 2 | -6.347 | -3.278 | |||
102 | NM_003256 | A | WNT |
TIMP4
| Tissue inhibitor of metalloproteinase 4 | -6.319 | -3.250 |
TIMP4
| 0.08 | |
105 | NM_000698 | M |
ALOX5
| Arachidonate 5-lipoxygenase | 3.229 | 4.736 | ||||
106 | NM_014029 | B | OC |
RAC2
| Rho family, small GTP binding protein Rac2 | 3.227 | 5.325 | |||
108 | NM_003670 | B, C | OB, CB | TGF-β/BMP |
DEC1
| Differentially expressed in chondrocytes 1 | -3.203 | -3.783 | ||
109 | NM_002067 | B | OB |
GNA11
| Guanine nucleotide binding protein, alpha 11 | -4.353 | -3.202 | |||
115 | AF263545 | B | OB |
SLC14A1
| Solute carrier family 14, member 1 | 3.163 | 5.759 | |||
120 | NM_005127 | B | M |
CLECSF2
| C-type lectin domain family 2, member B | -7.330 | -3.141 | |||
123 | NM_004252 | B | WNT |
NHERF1
| Sodium/Hydrogen exchanger regulatory factor 1 | 5.280 | 3.138 |
NHERF1
| 1.71 | |
124 | NM_006186 | B | OB |
NR4A2
| Nuclear receptor subfamily 4, group A, member 2 | -3.128 | -3.354 | |||
133 | NM_000104 | B | OC |
CYP1B1
| Cytochrome P450, family 1, subfamily B, 1 | -3.075 | -5.148 | |||
136 | NM_003005 | B |
SELP
| Selectin P | 8.740 | 3.066 | ||||
139 | NM_004334 | B | OC |
BST1
| Bone marrow stromal cell antigen 1 (CD157) | 3.037 | 3.601 | |||
141 | AK023619 | A |
CRIM1
| Cysteine-rich motor neuron 1 | -3.043 | -3.271 | ||||
143 | NM_013332 | A | WNT |
HIG2
| Hypoxia-inducible protein 2 | -6.019 | -3.035 | |||
144 | NM_001845 | A, B | TGF-β/BMP |
COL4A1
| Collagen, type IV, alpha 1 | -3.028 | -8.960 |
COL4A1
| 0.57 | |
146 | NM_016224 | A, B | OB | WNT |
SNX9
| Sorting nexin 9 | -3.025 | -6.086 |
Altered expression of WNT and TGF-β/BMP signalling pathway component and target genes in OA bone
Real-time PCR | ||||||||
---|---|---|---|---|---|---|---|---|
GenBank | Role | Cell type | Symbol | Name | t OA/CTL | t OA/OP | Symbol | OA/CTL |
WNT pathway components and modulators | ||||||||
AY009399 | B, C | OB, OC, CB |
WNT5B
| Wingless-type MMTV integration site family, member 5B | 3.719 | 0.717 |
WNT5B
| 2.52 |
NM_002332 | A, B, C | OB, OC, CB |
LRP1
| Low density lipoprotein-related protein 1 | 3.062 | -7.071 | ||
NM_002333 |
LRP3
| Low density lipoprotein-related protein 3 | 5.950 | 1.146 | ||||
NM_017412 |
FZD3
| Frizzled homolog 3 | -3.677 | 0.835 | ||||
AF086500 |
FZD8
| Frizzled homolog 8 | 3.024 | -1.557 | ||||
NM_003015 |
SFRP5
| Secreted frizzled-related protein 5 | -4.338 | 1.154 | ||||
NM_004655 |
AXIN2
| Axin 2 | -3.123 | 2.490 | ||||
NM_000038 |
APC
| Adenomatosis polyposis coli | -5.171 | 1.155 | ||||
AK023892 |
DAAM1
| Dishevelled associated activator of morphogenesis 1 | -6.704 | 2.850 | ||||
NM_000314 | A, B | OB, OC |
PTEN
| Phosphatase and tensin homolog | -5.288 | -0.216 |
PTEN
| 0.30 |
AF028823 |
TIP1
| Tax interaction protein 1 | 5.057 | -5.674 | ||||
AB006630 |
TCF20
| Transcription factor 20 | 8.559 | 2.719 | ||||
AK026898 | B | M |
FOXP1
| Forkhead box P1 | -5.122 | 1.761 | ||
WNT inducible/target genes | ||||||||
NM_000591 | B | OB, OC, M |
CD14
| CD14 antigen | 5.965 | -7.036 |
CD14
| 3.47 |
NM_004039 | A, B | OB, OC, M |
ANXA2
| Annexin A2 | 5.716 | -7.601 | ||
NM_000211 | B | OC |
ITGB2
| Integrin, beta 2 (CD18) | 6.104 | -1.243 |
ITGB2
| 2.95 |
NM_018456 |
EAF2
| ELL associated factor 2 | 6.450 | 0.884 | ||||
NM_000041 | B | OB, M |
APOE
| Apolipoprotein E | 6.896 | -2.391 | ||
AB012643 | B | OB |
ALPL
| Alkaline phosphatase, liver/bone/kidney | -5.942 | -1.213 | ||
NM_002229 | B | OB |
JUNB
| Jun B proto-oncogene | 5.053 | -3.804 | ||
NM_003377 | A, B |
VEGFB
| Vascular endothelial growth factor B | 3.238 | -3.772 | |||
NM_005429 | A, B |
VEGFC
| Vascular endothelial growth factor C | 5.304 | 0.473 | |||
NM_000963 | B | OB |
PTGS2
| Prostaglandin-endoperoxide synthase 2 | 4.346 | -0.842 | ||
NM_005194 | B | OB |
CEBPB
| CCAAT/enhancer binding protein, beta | 4.273 | -4.092 | ||
AL353944 | A, B | OB |
ID1
| Inhibitor of DNA binding 1 | 3.923 | -1.996 | ||
NM_000900 | B | OB |
MGP
| Matrix Gla protein | 2.791 | -3.073 | ||
M14584 | A, B, C | OB, OC, CB |
IL6
| Interleukin 6 | 2.589 | -3.612 | ||
NM_006350 | B, C | OB, CB |
FST
| Follistatin | -2.137 | -7.912 | FST | 0.38 |
AL353944 | B | OB |
RUNX2
| Runt-related transcription factor 2 | 1.611 | 1.050 | RUNX2 | 2.07 |
TGF-β/BMP pathway components and modulators | ||||||||
M38449 | A, B, C | OB, OC, CB |
TGFB1
| Transforming growth factor, beta 1 | 2.739 | 3.054 | ||
AK021486 | B, C | OB, CB |
BMP5
| Bone morphogenetic protein 5 | -10.314 | -2.263 | ||
NM_002192 | A, B, C | OB, OC, CB |
INHBA
| Inhibin, beta A | -7.699 | -0.389 |
INHBA
| 0.31 |
NM_006350 | B, C | OB, CB |
FST
| Follistatin | -2.137 | -7.912 |
FST
| 0.38 |
NM_004612 | B |
TGFBR1
| Transforming growth factor, beta receptor I | -4.915 | 1.049 | |||
NM_000118 | A |
ENG
| Endoglin | 4.131 | -2.461 | |||
NM_001105 | B | OB |
ACVR1
| Activin A receptor, type I | 3.791 | -0.941 | ||
NM_003573 |
LTBP4
| Latent transforming growth factor beta binding protein 4 | -4.060 | 2.623 | ||||
NM_005902 | A, B | OB |
SMAD3
| SMAD, mothers against DPP homolog 3 | 4.119 | -3.582 |
SMAD3
| 2.64 |
NM_005359 | A, B | OB |
SMAD4
| SMAD, mothers against DPP homolog 4 | 3.957 | 0.156 | ||
NM_002165 | A, B | OB |
ID1
| Inhibitor of DNA binding 1 | 3.923 | -1.996 | ||
NM_002229 | B | OB |
JUNB
| Jun B proto-oncogene | 5.053 | -3.804 | ||
NM_005655 | B | OB |
KLF10
| Kruppel-like factor 10 | 4.443 | -4.449 | ||
NM_006037 | B | OB |
HDAC4
| Histone deacetylase 4 | 8.475 | 2.468 | ||
NM_000168 | B | OB |
GLI3
| GLI-Kruppel family member GLI3 | -4.675 | -0.298 | ||
AL353944 | B | OB |
RUNX2
| Runt-related transcription factor 2 | 1.611 | 1.050 |
RUNX2
| 2.07 |
TGF-β/BMP inducible/target genes | ||||||||
AK001052 | B | OB | FGFR1 | Fibroblast growth factor receptor 1 | 4.234 | 1.993 | ||
NM_001553 | A | IGFBP7 | Insulin-like growth factor binding protein 7 | 5.137 | -6.302 | |||
NM_000211 | B | OC | ITGB2 | Integrin, beta 2 (CD18) | 6.104 | -1.243 | ITGB2 | 2.95 |
AK001060 | B, C | OB, CB | DCN | Decorin | -6.325 | 2.628 | ||
NM_000177 | B | OC | GSN | Gelsolin | 4.725 | -2.387 | ||
X55525 | B | OB | COL1A2 | Collagen, type I, alpha 2 | 5.538 | -3.633 | ||
NM_003118 | A, B | OB | SPARC | Secreted protein, acidic, cysteine-rich | 3.188 | -1.844 | ||
NM_004407 | B | OB, OS | DMP1 | Dentin matrix acidic phosphoprotein | -3.523 | -1.397 | ||
NM_001831 | A, B | CLU | Clusterin | 4.803 | -2.030 | |||
Not represented on Compugen human 19K microarray | ||||||||
NM_001904 | A, B | OB, OC |
CTNNB1
| Catenin beta 1 |
CTNNB1
| 2.38 |
Identification of differentially expressed OA genes between females and males
GenBank | Role | Cell type | Symbol | Name | t OAF/OAM | t OA/CTL | t OA/OP |
---|---|---|---|---|---|---|---|
Differentially expressed genes in top 20 regulated genes | |||||||
NM_000177 | B | OC |
GSN
| Gelsolin | 5.983 | 4.725 | -2.387 |
NM_001078 | B | OB, OC |
VCAM1
| Vascular cell adhesion molecule 1 | 5.158 | -1.358 | -2.377 |
NM_006764 |
IFRD2
| Interferon-related developmental regulator 2 | -5.081 | 4.274 | 2.162 | ||
NM_018456 |
EAF2
| ELL associated factor 2 | 4.574 | 6.450 | 0.884 | ||
NM_002087 | B | OC |
GRN
| Granulin | 4.562 | 11.161 | -2.008 |
NM_000211 | B | OC |
ITGB2
| Integrin, beta 2 (CD18) | 4.378 | 6.104 | -1.243 |
NM_004203 |
PKMYT1
| Protein kinase, membrane associated tyrosine/threonine 1 | -4.373 | -3.375 | 1.741 | ||
NM_001329 |
CTBP2
| C-terminal binding protein 2 | -4.339 | 1.548 | 4.057 | ||
NM_006202 | B | OB, OC |
PDE4A
| Phosphodiesterase 4A | -4.131 | -1.565 | 3.337 |
NM_017845 |
COMMD8
| COMM domain containing 8 | 4.118 | 3.264 | -0.398 | ||
AY009399 | B, C | OB, OC, CB |
WNT5B
| Wingless-type MMTV integration site family, member 5B | 4.107 | 3.719 | 0.717 |
NM_002822 | B | OC |
PTK9
| PTK9 protein tyrosine kinase 9 | 4.099 | -0.597 | -5.894 |
NM_002343 | B | OB |
LTF
| Lactotransferrin | 4.096 | 4.918 | 1.882 |
Additional differentially expressed genes in top 50 regulated genes | |||||||
NM_005606 | A, B | OB, OC |
LGMN
| Legumain | 3.853 | 9.631 | -4.470 |
NM_015946 | A, B, C | OB, CB |
ITGA1
| Integrin, alpha 1 | 3.813 | 3.904 | 0.131 |
NM_004039 | B | OB, OC |
ANXA2
| Annexin A2 | 3.754 | 5.716 | -7.601 |
M14087 | A, B | OB |
LGALS1
| Lectin, galactoside-binding, soluble, | 3.705 | 4.583 | -0.045 |
NM_006079 | A, B | OB |
CITED2
| Cbp/p300-interacting transactivator with Glu/Asp-rich domain 2 | 3.591 | 8.580 | -1.403 |
M38449 | A, B, C | OB, OC, CB |
TGFB1
| Transforming growth factor, beta 1 | -3.575 | 2.739 | 3.054 |
Z15114 | A, B | OB |
PRKCG
| Protein kinase C, gamma | -3.570 | 0.018 | 3.741 |
NM_003639 | B | OC |
IKBKG
| I kappa B kinase gamma | 3.376 | 6.775 | -1.704 |
AK026898 | B | OC |
FOXP1
| Forkhead box P1 | -3.348 | -5.122 | 1.761 |
NM_001928 | B | OB |
DF
| D component of complement (adipsin) | 3.306 | 6.851 | -0.991 |
NM_006037 | B | OB |
HDAC4
| Histone deacetylase 4 | 3.272 | 8.475 | 2.468 |
NM_001742 | B | OC |
CALCR
| Calcitonin receptor | -3.036 | 0.663 | 1.800 |
Not detected by microarray to be differentially regulated between females and males | |||||||
NM_004142 | A, B, C | OB, OC, CB |
MMP25
| Matrix metalloproteinase 25 | 0.237 | 4.942 | 7.183 |
Discussion
Gene | Description/function | References |
---|---|---|
Bone remodeling, osteoblast: upregulated in osteoarthritis (OA) bone | ||
S100A4 | Negative regulator of matrix mineralization in osteoblasts | [88,89] |
MMP25 | Metalloproteinase with role in matrix metalloproteinase (MMP)2 activation. Mice lacking MMP2 have disrupted osteocytes and altered bone mineralization | [59,60] |
Bone remodeling, osteoblast: downregulated in OA bone | ||
MEPE | Extracellular matrix protein, highly expressed in osteocytes | [58] |
IBSP | Major constituent of the bone matrix, thought to initiate and regulate mineralization | [90] |
MT2A | Metallothionein proteins (also MT1L and MT1G) have roles in regulating osteoblast differentiation and mineralization | [91,92] |
ADM | Adrenomedullin stimulates osteoblast activity, but also interacts with and influences the effects of key bone regulators insulin-like growth factor (IGF)1 and transforming growth factor (TGF)-β | [93,94] |
STC1 | Stanniocalcin inhibits calcium uptake and has inhibitory effect on bone growth during development | [95,96] |
IGFBP3 | Constitutive over-expression of IGF1-binding protein (IGFBP)3 impairs osteoblast proliferation and bone formation | [97] |
GADD45B | Mice deficient in GADD45B protein have defective bone mineralization | [98] |
ADAMTS4 | Metalloproteinase involved in remodelling extracellular matrix. Upregulated in fracture healing. Expressed in osteocytes and osteoblasts | [99,100] |
LTF | Lactotransferrin is an anabolic bone factor | [101] |
DF | Adipsin inhibits osteoblastogenesis | [102] |
Bone remodeling, osteoclast: upregulated in OA bone | ||
ADAM8 | Stimulatory role in osteoclast formation and differentiation | [103] |
CCR2 | Receptor for CC chemokine ligand (CCL)2, which promotes recruitment and fusion of monocytes/osteoclast precursors | [104] |
RAC2 | Member of the Rho-GTPase subfamily. Involved in organisation of cytoskeleton and adhesion of osteoclasts to bone | [105] |
CD14 | Monocyte/osteoclast precursor marker. CD14-deficient mice have increased bone mass | [106,107] |
ANXA2 | Stimulates osteoclast precursor proliferation and differentiation through production of granulocyte-macrophage colony-stimulating factor (GMCSF) and receptor activator of nuclear factor-kB ligand (RANKL) | [108] |
GSN | Gelsolin deficiency in mice blocks podosome assembly in osteoclasts and produces increased bone mass | [109] |
ITGB2 | Adhesion molecule important in cell-to-cell contacts during the early stage of osteoclast development | [110,111] |
Bone remodeling, osteoclast: downregulated in OA bone | ||
IGFBP3 | Over-expression of IGFBP3 in mice increases osteoclast number and bone resorption | [97] |
STC1 | Stanniocalcin suppresses osteoclast activity | [96] |
PTEN | Over-expression of PTEN suppresses RANKL-stimulated signal transduction during osteoclast differentiation | [112] |
FOXP1 | Transcriptional repressor that has role in modulating monocyte differentiation | [113] |
PDE4A | Down-regulated during monocyte to macrophage/osteoclast differentiation | [114] |
WNT pathway components and modulators: upregulated in OA bone | ||
WNT5B | WNT ligand with roles in osteoblastogenic and chondrogenic differentiation | [68,69,70] |
CTNNB1 | Mice lacking b-catenin in osteoblasts develop severe osteopenia with increased osteoclastogenesis and impaired osteoblastogenesis | [115] |
AKT3 | Member of the AKT kinase family. Role in regulating osteoblast lifespan | [116,117] |
NHERF1 | Mediates parathyroid hormone receptor signalling. Interacts with b-catenin, potentiating the effects of parathyroid hormone (PTH) on WNT signalling in bone. | [118,119] |
WNT pathway components and modulators: downregulated in OA bone | ||
FZD3 | WNT5B co-receptor | [120] |
PTEN | Modulates/antagonises WNT signalling. Roles in osteoclast and osteoblast differentiation | [112,117] |
APC | Loss of APC in mice leads to increased bone mass | [115] |
AXIN2 | Negatively regulates both expansion of osteoprogenitors and maturation of osteoblasts through its modulation of WNT signalling | [121] |
TGF-β/bone morphogenic protein (BMP) pathway components and modulators: upregulated in OA bone | ||
ACVR1 | BMP and activin A receptor. Mutation in receptor causes ectopic osteogenesis | [122] |
SMAD3 | Important mediator of TGF-β signalling and regulator of osteoblastogenesis and bone formation | [80,82] |
ID1 | Transcription factor with roles in bone formation and osteoblast proliferation and differentiation | [123] |
RUNX2 | Key transcription factor involved in promoting osteoblast differentiation | [76] |
TGF-β/BMP pathway components and modulators: downregulated in OA bone | ||
TGFB1 | Growth factor with key role in regulating bone development and metabolism | [34,80] |
INHBA | TGF-β family member. Can act as either inhibitor or activator of bone formation and osteoblast differentiation | [124,125] |
BMP5 | Secreted signalling molecule involved in skeletal development and genetically implicated in OA | [29] |
FST | TGF-β/BMP antagonist that inhibits osteoblast differentiation | [126] |