RhoA activation and nuclearization marks loss of chondrocyte phenotype in crosstalk with Wnt pathway

Öztürk, Ece; Despot-Slade, Evelin; Pichler, Michael; Zenobi‐Wong, Marcy

doi:10.1016/j.yexcr.2017.08.033

Cited by 16 publications

(15 citation statements)

References 57 publications

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“…Utilizing the mouse chondroprogenitor ATDC5 cell line, Yang et al (2017) also demonstrated that YAP overexpression promotes chondrocyte proliferation, but inhibits chondrocyte differentiation through the Wnt/β-catenin signaling pathway. The role of Wnt/β-catenin signaling in suppressing chondrogenic differentiation was confirmed by Öztürk et al (2017) , who showed that β-catenin is upregulated in de-differentiating chondrocytes. Öztürk et al (2017) also observed that chondrocyte de-differentiation is accompanied by increased RhoA activity.…”

Section: Modulation Of Stem/progenitor Cell Lineage Fate By Yap/tazmentioning

confidence: 90%

“…The role of Wnt/β-catenin signaling in suppressing chondrogenic differentiation was confirmed by Öztürk et al (2017) , who showed that β-catenin is upregulated in de-differentiating chondrocytes. Öztürk et al (2017) also observed that chondrocyte de-differentiation is accompanied by increased RhoA activity.…”

Section: Modulation Of Stem/progenitor Cell Lineage Fate By Yap/tazmentioning

confidence: 90%

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Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways

Heng

Zhang

Aubel

et al. 2020

Front. Cell Dev. Biol.

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The penultimate effectors of the Hippo signaling pathways YAP and TAZ, are transcriptional co-activator proteins that play key roles in many diverse biological processes, ranging from cell proliferation, tumorigenesis, mechanosensing and cell lineage fate determination, to wound healing and regeneration. In this review, we discuss the regulatory mechanisms by which YAP/TAZ control stem/progenitor cell differentiation into the various major lineages that are of interest to tissue engineering and regenerative medicine applications. Of particular interest is the key role of YAP/TAZ in maintaining the delicate balance between quiescence, self-renewal, proliferation and differentiation of endogenous adult stem cells within various tissues/organs during early development, normal homeostasis and regeneration/healing. Finally, we will consider how increasing knowledge of YAP/TAZ signaling might influence the trajectory of future progress in regenerative medicine.

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Section: Modulation Of Stem/progenitor Cell Lineage Fate By Yap/tazmentioning

confidence: 90%

Section: Modulation Of Stem/progenitor Cell Lineage Fate By Yap/tazmentioning

confidence: 90%

Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways

Heng

Zhang

Aubel

et al. 2020

Front. Cell Dev. Biol.

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“…In chondrocytes, the effects of wnt3a are described repeatedly to stimulate chondrogenic dedifferentiation. 13,27,[45][46][47][48][49][58][59][60] The origin of the chondrocytes studied ranged from humans, large animals (i.e., bovine), to smaller animals (i.e., rat or chicken). Despite the differences in the supplementation method and the origin of the cells, all articles reported either a loss of chondrogenic gene marker expression, decreased proteoglycan production or a combination of these.…”

Section: Chondrocytesmentioning

confidence: 99%

“…13,21 Interestingly, in combination with other growth factors; e.g., fibroblast growth factor (FGF), 22 transforming growth factor (TGF)-β, 23,24 and bone morphogenetic protein (BMP) 25,26 family, wnt3a appears to be beneficial for MSCs to adopt a chondrogenic phenotype in 2-dimensional, and 3-dimensional cultures. 23,27 Whether wnt3a and wnt5a are in fact beneficial for chondrogenesis remains arguable, however, their presence in cartilage-based tissues is undisputable, raising interest on the potential induction capacity of wnt3a/wnt5a on the cartilage-based NP. Therefore, it is considered valuable to reach a consensus on wnt3a and wnt5a in chondrogenesis for regeneration of the IVD.…”

Section: Introductionmentioning

confidence: 99%

Wnt3a and wnt5a as Potential Chondrogenic Stimulators for Nucleus Pulposus Cell Induction: A Comprehensive Review

et al. 2020

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Low back pain remains a highly prevalent pathology engendering a tremendous socioeconomic burden. Low back pain is generally associated with intervertebral disc (IVD) degeneration, a process involving the deterioration of nucleus pulpous (NP) cells and IVD matrix. Scientific interest has directed efforts to restoring cell numbers as a strategy to enable IVD regeneration. Currently, mesenchymal stromal cells (MSCs) are being explored as cell therapy agents, due to their easy accessibility and differentiation potential. For enhancement of MSCs, growth factor supplementation is commonly applied to induce differentiation towards a chondrogenic (NP) cell phenotype. The wnt signaling pathways play a crucial role in chondrogenesis, nonetheless, literature appears to present controversies with regard to wnt3a and wnt5a for the induction of NP cells, chondrocytes, and MSCs. This review aims to summarize the reporting on wnt3a/wnt5a mediated NP cell differentiation, and to elucidate the mechanisms involved in wnt3a and wnt5a mediated chondrogenesis for potential application as cell therapy supplements for IVD regeneration. Our review suggests that wnt3a, subsequently replaced with a chondrogenic stimulating growth factor, can enhance the chondrogenic potential of MSCs in vitro. Contrariwise, wnt5a is suggested to play a role in maintaining cell potency of differentiated NP or chondrogenic cells.

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“…In addition to preventing nuclear accumulation of MRTF‐A, CCG‐1423 has also been implicated in inhibition of RhoA‐mediated transcription . RhoA is another member of the Rho GTPase family which plays a context‐dependent role in regulating the chondrocyte phenotype and has been shown to intersect with Wnt effectors beta‐catenin and Yes‐associated protein (YAP) and transcriptional co‐activator with PDZ‐binding motif (TAZ) . YAP/TAZ are two structurally similar actin‐regulated transcription factors involved in the canonical Hippo pathway and non‐canonical pathways.…”

Section: Discussionmentioning

confidence: 99%

CDC42 regulates the expression of superficial zone molecules in part through the actin cytoskeleton and myocardin‐related transcription factor‐A

Delve

Parreno

et al. 2018

Journal Orthopaedic Research

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Osteoarthritis (OA) is a degenerative disease that initially manifests as loss of the superficial zone (SZ) of articular cartilage. SZ chondrocytes (SZC) differ in morphology from other chondrocytes as they are elongated and oriented parallel to the tissue surface. Proteoglycan 4 (PRG4) and tenascin C (TNC) are molecules expressed by SZC, which have been shown to be chondroprotective. Identification of the signalling pathway(s) regulating expression of SZ molecules may lead to a therapeutic target that can be used to delay or prevent the onset of OA. The hypothesis of this study is that expression of SZ molecules are regulated in part, by the CDC42-actin-myocardin-related transcription factor-A (MRTF-A) signaling pathway. SZC from bovine metacarpal-phalangeal joints were isolated and grown in monolayer culture. Each target in the CDC42-actin-MRTF-A pathway was inhibited and the effect on cell shape, actin cytoskeleton status, and expression of PRG4 and TNC were determined. Treatment with the CDC42 inhibitor ML141 decreased PRG4 and TNC expression, and correlated with increased cell circularity and G-/F-actin ratio. PRG4 and TNC expression were differentially regulated by actin depolymerizing agents, latrunculin B and cytochalasin D. Chemical inhibition of MRTF-A resulted in decreased expression of both PRG4 and TNC; however, specific knockdown by small interfering RNA only decreased expression of TNC indicating that TNC, but not PRG4, is regulated by MRTF-A. Although PRG4 and TNC expression are both regulated by CDC42 and actin, it appears to occur through different downstream signaling pathways. Further study is required to elucidate the pathway regulating PRG4. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2421-2430, 2018.

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RhoA activation and nuclearization marks loss of chondrocyte phenotype in crosstalk with Wnt pathway

Cited by 16 publications

References 57 publications

Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways

Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways

Wnt3a and wnt5a as Potential Chondrogenic Stimulators for Nucleus Pulposus Cell Induction: A Comprehensive Review

CDC42 regulates the expression of superficial zone molecules in part through the actin cytoskeleton and myocardin‐related transcription factor‐A

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