Ser/Thr-phosphoprotein phosphatases in chondrogenesis: neglected components of a two-player game

Matta, Csaba; Mobasheri, Ali; Gergely, Pál; Zákány, Róza

doi:10.1016/j.cellsig.2014.06.013

Cited by 18 publications

(22 citation statements)

References 102 publications

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“…In vitro, HDAC4 can form a complex with PP2A, and PP2A controls HDAC4 nuclear import via the dephosphorylation of multiple serines including the 14-3-3 binding sites and serine 298. [20, 32, 33]. Our study suggests that compression induces HDAC4 nuclear import through stimulation of PP2A activity and dephosphorylation of HDAC4 in chondrocytes.…”

Section: Discussionmentioning

confidence: 68%

“…Our study suggests that compression induces HDAC4 nuclear import through stimulation of PP2A activity and dephosphorylation of HDAC4 in chondrocytes. To further validate this finding, chondrocytes were treated with 1 nM Okadaic Acid (OA) at which concentration PP2A is completely inhibited by OA[31-33]. As expected, pre-treatment of chondrocytes with the PP2A-specific inhibitor, OA, results in the loss of stimulation of PP2A activity, the loss of reduction of Ps-HDAC4, the loss of translocation of HDAC4 from cytoplasm to the nucleus, and the loss of regulation of chondrocytes gene expression after compression.…”

Section: Discussionmentioning

confidence: 99%

“…Okadaic acid (OA) (Sigma), a specific inhibitor for PP2A[31-33], was prepared as a 10-μM stock in dimethyl sulfoxide (DMSO, Sigma) and added to culture medium 2 hours before compression at the final concentration of 1nM. The concentration can completely inhibited PP2A activity[31, 33].…”

Section: Methodsmentioning

confidence: 99%

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Compression regulates gene expression of chondrocytes through HDAC4 nuclear relocation via PP2A-dependent HDAC4 dephosphorylation

Chen

Wei

Wang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Biomechanics play a critical role in the modulation of chondrocyte function. The mechanisms by which mechanical loading is transduced into intracellular signals that regulate chondrocyte gene expression remain largely unknown. Histone deacetylase 4 (HDAC4) is specifically expressed in chondrocytes. Mice lacking HDAC4 display chondrocyte hypertrophy, ectopic and premature ossification, and die early during the perinatal period. HDAC4 has a remarkable ability to translocate between the cell's cytoplasm and nucleus. It has been established that subcellular relocation of HDAC4 plays a critical role in chondrocyte differentiation and proliferation. However, it remains unclear whether subcellular relocation of HDAC4 in chondrocytes can be induced by mechanical loading. In this study, we first report that compressive loading induces HDAC4 relocation from the cytoplasm to the nucleus of chondrocytes via stimulation of Ser/Thr-phosphoprotein phosphatases 2A (PP2A) activity, which results in dephosphorylation of HDAC4. Dephosphorylated HDAC4 relocates to the nucleus to achieve transcriptional repression of Runx2 and regulates chondrocyte gene expression in response to compression. Our results elucidate the mechanism by which mechanical compression regulates chondrocyte gene expression through HDAC4 relocation from the cell's cytoplasm to the nucleus via PP2A-depended HDAC4 dephosphorylation.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Compression regulates gene expression of chondrocytes through HDAC4 nuclear relocation via PP2A-dependent HDAC4 dephosphorylation

Chen

Wei

Wang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…PAC1 receptor activation can be responsible for the elevation of intracellular Ca 2+ concentration and ultimately can regulate the Ca 2+ dependent protein phosphatase PP2B (also known as calcineurin). This enzyme is one of the positive regulators of in vitro chondrogenesis [35,41,43]. Therefore, we investigated the involvement of this Ser/Thr phosphatase in PACAP signaling pathways and connection between PP2B activity and PACAP signaling was proved [17] (Fig.…”

Section: Regulation Of Chondrogenesis Focused On Vip and Pacapmentioning

confidence: 99%

PACAP and VIP signaling in chondrogenesis and osteogenesis

et al. 2015

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“…Reversible protein phosphorylation on specific Ser/Thr residues regulated by the balanced activities of protein kinases and phosphoprotein phosphatases is a key process that controls all stages and aspects of the chondrocyte life cycle in response to extracellular stimuli [25,26]. Amongst the key chondrocyte signaling pathways are protein kinase A, protein kinase C, mitogen-activated protein kinases (MAPKs, such as p38, JNK, and ERK), the phosphoinositide-3 kinase (PI3K)/Akt pathway, as well as protein phosphatase 1A (PP1A), PP2A, and calcineurin (PP2B) [27].…”

Section: Alterations In Protein Kinase and Phosphoprotein Phosphatasementioning

confidence: 99%

Age-Related Alterations in Signaling Pathways in Articular Chondrocytes: Implications for the Pathogenesis and Progression of Osteoarthritis - A Mini-Review

2016

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Musculoskeletal conditions are a major burden on individuals, healthcare systems, and social care systems throughout the world, with indirect costs having a predominant economic impact. Aging is a major contributing factor to the development and progression of arthritic and musculoskeletal diseases. Indeed, aging and inflammation (often referred to as ‘inflammaging') are critical risk factors for the development of osteoarthritis (OA), which is one of the most common forms of joint disease. The term ‘chondrosenescence' has recently been introduced to define the age-dependent deterioration of chondrocyte function and how it undermines cartilage function in OA. An important component of chondrosenescence is the age-related deregulation of subcellular signaling pathways in chondrocytes. This mini-review discusses the role of age-related alterations in chondrocyte signaling pathways. We focus our attention on two major areas: age-dependent alterations in transforming growth factor-β signaling and changes in protein kinase and phosphoprotein phosphatase activities in aging chondrocytes. A better understanding of the basic signaling mechanisms underlying aging in chondrocytes is likely to facilitate the development of new therapeutic and preventive strategies for OA and a range of other age-related osteoarticular disorders.

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Ser/Thr-phosphoprotein phosphatases in chondrogenesis: neglected components of a two-player game

Abstract: Protein phosphorylation plays a determining role in the regulation of chondrogenesis in vitro.

Cited by 18 publications

References 102 publications

Compression regulates gene expression of chondrocytes through HDAC4 nuclear relocation via PP2A-dependent HDAC4 dephosphorylation

Compression regulates gene expression of chondrocytes through HDAC4 nuclear relocation via PP2A-dependent HDAC4 dephosphorylation

PACAP and VIP signaling in chondrogenesis and osteogenesis

Age-Related Alterations in Signaling Pathways in Articular Chondrocytes: Implications for the Pathogenesis and Progression of Osteoarthritis - A Mini-Review

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