Corrigendum: WNT5B in Physiology and Disease

Suthon, Sarocha; Perkins, Rachel S.; Bryja, Vı́tězslav; Miranda-Carboni, Gustavo A.; Krum, Susan A.

doi:10.3389/fcell.2021.724948

Cited by 2 publications

(1 citation statement)

References 8 publications

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“…These two ligands signal through the noncanonical pathway. While WNT5A and WNT5B are highly similar in structure, they have different functions in chondrocytes 26 . WNT5A induces cytokine production and senescence, whereas WNT5B stimulates collagen type I secretion and is responsible for inhibiting the production of ECM components and chondrocyte differentiation 27,28 .…”

Section: Discussionmentioning

confidence: 99%

Mechanical stress and inflammation have opposite effects on Wnt signaling in human chondrocytes

Timmermans

Blom

Nelissen

et al. 2023

Journal Orthopaedic Research

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Dysregulation of Wingless and Int‐1 (Wnt) signaling has been strongly associated with development and progression of osteoarthritis (OA). Here, we set out to investigate the independent effects of either mechanical stress (MS) or inflammation on Wnt signaling in human neocartilage pellets, and to relate this Wnt signaling to OA pathophysiology. OA synovium‐conditioned media (OAS‐CM) was collected after incubating synovium from human end‐stage OA joints for 24 h in medium. Cytokine levels in the OAS‐CM were determined with a multiplex immunoassay (Luminex). Human neocartilage pellets were exposed to 20% MS, 2% OAS‐CM or 1 ng/mL Interleukin‐1β (IL‐1β). Effects on expression levels of Wnt signaling members were determined by reverse transcription‐quantitative polymerase chain reaction. Additionally, the expression of these members in articular cartilage from human OA joints was analyzed in association with joint space narrowing (JSN) and osteophyte scores. Protein levels of IL‐1β, IL‐6, IL‐8, IL‐10, tumor necrosis factor α, and granulocyte‐macrophage colony‐stimulating factor positively correlated with each other. MS increased noncanonical WNT5A and FOS expression. In contrast, these genes were downregulated upon stimulation with OAS‐CM or IL‐1β. Furthermore, Wnt inhibitors DKK1 and FRZB decreased in response to OAS‐CM or IL‐1β exposure. Finally, expression of WNT5A in OA articular cartilage was associated with increased JSN scores, but not osteophyte scores. Our results demonstrate that MS and inflammatory stimuli have opposite effects on canonical and noncanonical Wnt signaling in human neocartilage. Considering the extent to which MS and inflammation contribute to OA in individual patients, we hypothesize that targeting specific Wnt pathways offers a more effective, individualized approach.

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Section: Discussionmentioning

confidence: 99%

Mechanical stress and inflammation have opposite effects on Wnt signaling in human chondrocytes

Timmermans

Blom

Nelissen

et al. 2023

Journal Orthopaedic Research

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Targeting WNT5B and WNT10B in osteosarcoma

Miranda-Carboni,

Krum

2024

Oncotarget

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WNT signaling regulates osteosarcoma proliferation. However, there is controversy in the field of osteosarcoma as to whether WNT signaling is pro- or anti-tumorigenic. WNT-targeting therapeutics, both activators and inhibitors, are compared. WNT5B, a β-catenin-independent ligand, and WNT10B, a β-catenin-dependent WNT ligand, are each expressed in osteosarcomas, but they are not expressed in the same tumors. Furthermore, WNT10B and WNT5B regulate different histological subtypes of osteosarcomas. Using WNT signaling modulators as therapeutics may depend on the WNT ligand and/or the activated signaling pathway.

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Corrigendum: WNT5B in Physiology and Disease

Cited by 2 publications

References 8 publications

Mechanical stress and inflammation have opposite effects on Wnt signaling in human chondrocytes

Mechanical stress and inflammation have opposite effects on Wnt signaling in human chondrocytes

Targeting WNT5B and WNT10B in osteosarcoma

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