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

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]