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Table 6 Bone related-functions of a selection of differentially expressed genes in osteoarthritis bone

From: Microarray gene expression profiling of osteoarthritic bone suggests altered bone remodelling, WNT and transforming growth factor-β/bone morphogenic protein signalling

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]