Regulation of fibronectin and metalloproteinase expression by Wnt signaling in rheumatoid arthritis synoviocytes

Sen, Malini; Reifert, Jack; Lauterbach, Kevin; Wolf, Vladimir; Rubin, Jeffrey S.; Corr, Maripat; Carson, Dennis A.

doi:10.1002/art.10593

Cited by 88 publications

(66 citation statements)

References 43 publications

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“…In more developed joints of new born mice, expression of these proteins was restricted in the synovium, raising a possibility that Notch signaling pathway might control the differentiation and development of joints. In addition, it was recently reported that RSF expressed high levels of both Wnt and Frizzled, a receptor-ligand pair implicated in both limb bud and bone marrow stem cell development (Sen et al, 2002). In supporting our observations, Nakazawa et al (2001) reported that Notch-1 was overexpressed in rheumatoid synoviocytes and TNF induced nuclear translation of NICD in RSF.…”

Section: Discussionsupporting

confidence: 89%

Induction of Notch signaling by tumor necrosis factor in rheumatoid synovial fibroblasts

et al. 2003

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Section: Discussionsupporting

confidence: 89%

Induction of Notch signaling by tumor necrosis factor in rheumatoid synovial fibroblasts

et al. 2003

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“…In addition, it was recently shown that Sox9 in differentiated chondrocytes promotes the degradation of ␤-catenin (Akiyama et al 2004). Because constitutive activation of the canonical Wnt signaling pathway has been found in the fibroblastlike synoviocytes in rheumatoid arthritis and up-regulated Wnt signaling is associated with fibronectin and pro-matrix metalloproteinase 3 expression (Sen et al 2002), further understanding of the Wnt/␤-catenin signaling in joint formation will be important for elucidating a fundamental developmental process and identifying therapeutic targets for treating cartilage and joint diseases.…”

Section: Maintenance Of Joint Cartilagementioning

confidence: 99%

Wnt/β-catenin signaling is sufficient and necessary for synovial joint formation

Guo

Day²,

Jiang³

et al. 2004

Genes Dev.

374

353

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A critical step in skeletal morphogenesis is the formation of synovial joints, which define the relative size of discrete skeletal elements and are required for the mobility of vertebrates. We have found that several Wnt genes, including Wnt4, Wnt14, and Wnt16, were expressed in overlapping and complementary patterns in the developing synovial joints, where ␤-catenin protein levels and transcription activity were up-regulated. Removal of ␤-catenin early in mesenchymal progenitor cells promoted chondrocyte differentiation and blocked the activity of Wnt14 in joint formation. Ectopic expression of an activated form of ␤-catenin or Wnt14 in early differentiating chondrocytes induced ectopic joint formation both morphologically and molecularly. In contrast, genetic removal of ␤-catenin in chondrocytes led to joint fusion. These results demonstrate that the Wnt/␤-catenin signaling pathway is necessary and sufficient to induce early steps of synovial joint formation. Wnt4, Wnt14, and Wnt16 may play redundant roles in synovial joint induction by signaling through the ␤-catenin-mediated canonical Wnt pathway.[Keywords: Wnt; ␤-catenin; joint formation; skeletal development] Supplemental material is available at http://www.genesdev.org. Formation of synovial joints between different skeletal elements is essential for the mobility of vertebrates. The number and position of joints also determine characteristic skeletal patterns in each vertebrate species by defining the size and shape of skeletal elements. As alterations of early patterning signals often lead to changes in the position and number of joints in the developing limb (Dahn and Fallon 2000;Suzuki et al. 2004), understanding the regulation of joint formation in the limb will also provide critical insights into how early-limb patterning is linked to later skeletal morphogenesis at the molecular level.In the developing limb, studies of descriptive embryology have shown that skeletal elements form through temporally and spatially regulated processes that include mesenchymal condensation, elongation, branching, and/ or segmentation (Shubin and Alberch 1986). Most of the synovial joints in the limb form through segmentation of a pre-existing cartilage rod. For instance, in the developing forelimb, the initial de novo mesenchymal condensation forms the cartilage anlagen of the humerus, the growth and branching of which then produce a Y-shaped bifurcation. It is the segmentation of this Y-shaped cartilage primordium that forms the elbow joint that separates the radius and ulna from the humerus (Shubin and Alberch 1986).Synovial joint formation starts from the differentiation of newly differentiated chondrocytes into flattened and densely packed interzone cells (for review, see Archer et al. 2003), which express joint-specific markers such as Gdf5 and lose the expression of chondrocytespecific markers such as ColII (Craig et al. 1987;Nalin et al. 1995;Morrison et al. 1996;Storm and Kingsley 1996). Later in development, the interzone cells differentiate and form three laye...

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“…By contrast, inhibition of Wnt-5a/Fzd-5 signaling blocks RA synoviocyte activation by blocking cytokine production (69). Activation of canonical Wnt signaling also increases expression of degradative enzymes such as MMP-3 in the same cell system (70). Other components such as Wnt-7a (71) and Wnt-10B (72) are also detected in OA synovium.…”

Section: Correlated Expression Of Wnt Signaling Components In Ra and mentioning

confidence: 99%

Wnt signaling in cartilage development and degeneration

Chun¹,

Oh²,

Yang³

et al. 2008

BMB Reports

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Regulation of fibronectin and metalloproteinase expression by Wnt signaling in rheumatoid arthritis synoviocytes

Cited by 88 publications

References 43 publications

Induction of Notch signaling by tumor necrosis factor in rheumatoid synovial fibroblasts

Induction of Notch signaling by tumor necrosis factor in rheumatoid synovial fibroblasts

Wnt/β-catenin signaling is sufficient and necessary for synovial joint formation

Wnt signaling in cartilage development and degeneration

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