Table 6 |
||
|
Bone related-functions of a selection of differentially expressed genes in osteoarthritis bone |
||
|
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] |
|
|
||
|
Hopwood et al. Arthritis Research & Therapy 2007 9:R100 doi:10.1186/ar2301 |
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