YAP1 negatively regulates chondrocyte differentiation partly by activating the β-catenin signaling pathway

Yang, Bin; Sun, Hairong; Song, Frank M.; Yu, Miao; Wu, Yanru; Wang, Jiawei

doi:10.1016/j.biocel.2017.04.007

Cited by 47 publications

(41 citation statements)

References 41 publications

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“…However, during early stage of bone repair, cell proliferation of chondroprogenitor cells and early committed chondrocytes are increased with YAP expression. Similar results were obtained in ATDC5 cells 45 , and C3H10T1/2 cells 46 . In addition, a recent study also showed that YAP expression is upregulated in the Gdf5 -lineage cells in the synovium during cartilage repair 47 .…”

Section: Discussionsupporting

confidence: 87%

Reciprocal inhibition of YAP/TAZ and NF-κB regulates osteoarthritic cartilage degradation

et al. 2018

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Osteoarthritis is one of the leading causes of pain and disability in the aged population due to articular cartilage damage. This warrants investigation of signaling mechanisms that could protect cartilage from degeneration and degradation. Here we show in a murine model of experimental osteoarthritis that YAP activation by transgenic overexpression or by deletion of its upstream inhibitory kinases Mst1/2 preserves articular cartilage integrity, whereas deletion of YAP in chondrocytes promotes cartilage disruption. Our work shows that YAP is both necessary and sufficient for the maintenance of cartilage homeostasis in osteoarthritis. Mechanistically, inflammatory cytokines, such as TNFα or IL-1β, trigger YAP/TAZ degradation through TAK1-mediated phosphorylation. Furthermore, YAP directly interacts with TAK1 and attenuates NF-κB signaling by inhibiting substrate accessibility of TAK1. Our study establishes a reciprocal antagonism between Hippo-YAP/TAZ and NF-κB signaling in regulating the induction of matrix-degrading enzyme expression and cartilage degradation during osteoarthritis pathogenesis.

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Section: Discussionsupporting

confidence: 87%

Reciprocal inhibition of YAP/TAZ and NF-κB regulates osteoarthritic cartilage degradation

et al. 2018

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“…In addition, YAP1 may inhibit chondrocyte maturation and endochondral ossification during bone development and growth ( 43 ). YAP1 suppresses chondrogenic differentiation in MSCs, and the downregulation of YAP expression contributes to the chondrogenic differentiation of MSCs ( 22 ). However, the number of studies on the interaction between hypoxia and YAP is limited, particularly in chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, inhibition of the Hippo pathway results in YAP nuclear retention and activation of transcriptional activity ( 21 ). In addition to the Hippo signaling pathway, one previous study indicated that a number of signaling pathways interact with YAP protein and serve important roles in regulating YAP protein activation ( 22 ). To the best of our knowledge, the interaction between hypoxia and YAP has not been examined in growth plate chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia promotes maintenance of the chondrogenic phenotype in rat growth plate chondrocytes through the HIF-1α/YAP signaling pathway

Jing

et al. 2018

Int J Mol Med

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The Hippo-yes-associated protein (YAP) signaling pathway was previously identified to serve an important role in controlling chondrocyte differentiation and post-natal growth. Growth plate cartilage tissue is avascular, and hypoxia-inducible factor (HIF)-1α is essential for chondrocytes to maintain their chondrogenic phenotype in a hypoxic environment. In the present study, the role of hypoxia and HIF-1α in the regulation of YAP in chondrocytes was investigated. The data demonstrated that hypoxia promoted the maintenance of the chondrogenic phenotype, HIF-1α expression and YAP activation in chondrocytes in a time-dependent manner. Hypoxia promoted YAP activation in a Hippo-independent manner. Inhibiting the expression of HIF-1α decreased the activation of YAP and downregulated the expression of sex-determining region-box 9 protein (SOX9) under hypoxic conditions, while the upregulation of HIF-1α by cobalt chloride promoted the expression and nuclear translocation of YAP and upregulated the expression of SOX9 and collagen II chain under normoxic conditions. In addition, inhibition of YAP expression under hypoxia did not affect the expression of the HIF-1α signaling pathway, but inhibited the up-regulation of SOX9 expression caused by hypoxia. In addition, reoxygenation following hypoxia inhibited the activation of YAP caused by hypoxia in chondrocytes, whereas the upregulation of SOX9 and collagen II chain also appeared to be inhibited. In conclusion, the results of the present study demonstrated that hypoxia promoted YAP activation via HIF-1α. Therefore, the HIF-1α/YAP signaling axis may serve an important role in controlling growth plate chondrocyte differentiation and the maintenance of the chondrogenic phenotype in growth plate chondrocytes.

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“…Notably, YAP1 also promotes early chondrocyte proliferation by regulating SOX6 expression and inhibiting collagen type X (COL10A1) expression by interacting with Runx2 during chondrocyte maturation, thereby inhibiting chondrocyte maturation (Deng et al, 2016;Ying et al, 2018). YAP1 negatively regulates chondrocyte differentiation by activating the β-catenin signaling pathway, and YAP1 overexpression enhances chondrocyte proliferation but inhibits chondrocyte differentiation (Yang et al, 2017). In another study of cartilage differentiation (Nie et al, 2019), dasatinib treatment was observed to significantly upregulate the serine phosphorylation of YAP1 and downregulate the protein expression of YAP1 and TAZ in a dose-dependent manner, promoting cartilage gene differentiation of MSCs by promoting the serine phosphorylation of YAP1.…”

Section: High Yap1 Expression Inhibits Chondrocyte Differentiation In Oamentioning

confidence: 99%

Yes-Associated Protein 1: Role and Treatment Prospects in Orthopedic Degenerative Diseases

Xie

Xiao

Tang

et al. 2020

Front. Cell Dev. Biol.

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The Hippo/yes-associated protein 1 signaling pathway is an evolutionarily conserved signaling pathway. This signaling pathway is primarily involved in the regulation of stem cell self-renewal, organ size and tissue regeneration by regulating cell proliferation, differentiation and apoptosis. It plays an important role in embryonic development and tissue organ formation. Yes-associated protein 1 (YAP1) is a key transcription factor in the Hippo signaling pathway and is negatively regulated by this pathway. Changes in YAP1 expression levels affect the occurrence and development of a variety of tumors, but the specific mechanism associated with this phenomenon has not been thoroughly studied. Recently, several studies have described the role of YAP1 in osteoarthritis (OA). Indeed, YAP1 is involved in orthopedic degenerative diseases such as osteoporosis (OP) in addition to OA. In this review, we will summarize the significance of YAP1 in orthopedic degenerative diseases and discuss the potential of the targeted modulation of YAP1 for the treatment of these diseases.

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YAP1 negatively regulates chondrocyte differentiation partly by activating the β-catenin signaling pathway

Cited by 47 publications

References 41 publications

Reciprocal inhibition of YAP/TAZ and NF-κB regulates osteoarthritic cartilage degradation

Reciprocal inhibition of YAP/TAZ and NF-κB regulates osteoarthritic cartilage degradation

Hypoxia promotes maintenance of the chondrogenic phenotype in rat growth plate chondrocytes through the HIF-1α/YAP signaling pathway

Yes-Associated Protein 1: Role and Treatment Prospects in Orthopedic Degenerative Diseases

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