Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway in cultured human chondrocytes

Saito, Taichi; Nishida, Keiichiro; Furumatsu, Takayuki; Yoshida, Aki; Ozawa, Masatsugu; Ozaki, Toshifumi

doi:10.1016/j.joca.2012.09.003

Cited by 61 publications

(47 citation statements)

References 51 publications

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“…It is also reported that the expression of RUNX-2 contributes to increased expression of MMP-13 [16]. Our previous report demonstrated that RUNX-2 is an upstream regulator of the mechanical stress-induced ADAMTS-5 and MMP-13 [22,25].…”

Section: Discussionmentioning

confidence: 85%

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Hyaluronan suppresses mechanical stress-induced expression of catabolic enzymes by human chondrocytes via inhibition of IL-1β production and subsequent NF-κB activation

et al. 2015

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Section: Discussionmentioning

confidence: 85%

“…Using this apparatus, the entire silicon membrane can be stretched uniformly [23,24]. In the current study, a CTS (0.5 Hz, 10 % elongation) was applied for 30 min as described in our previous study [22,25]. Cells incubated without mechanical stress were used as control.…”

Section: Stretching Experimentsmentioning

confidence: 99%

Hyaluronan suppresses mechanical stress-induced expression of catabolic enzymes by human chondrocytes via inhibition of IL-1β production and subsequent NF-κB activation

et al. 2015

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“…Chemical inhibition of HDAC activity could improve osteogenic differentiation, suggesting both a direct acetylation-dependent [16,18], as well as a MAPKinase-dependent mechanism [19]. There is evidence that several HDACs affect the expression and activity of the key osteogenic transcription factor Runx2.…”

Section: Introductionmentioning

confidence: 99%

TGF-β1-Dependent Downregulation of HDAC9 Inhibits Maturation of Human Osteoblasts

Ehnert¹,

Heuberger²,

Nüssler³

et al. 2017

JFMK

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Abstract:Transforming growth factor β (TGF-β) is a key regulator of bone density. Recently, we have shown that TGF-β 1 effectively blocks bone morphogenetic protein-induced maturation of human osteoblasts (hOBs) in a histone deacetylase (HDAC)-dependent manner. To better understand the underlying mechanisms and to identify possible therapeutic targets, the current study aimed at characterizing the expression changes of different HDACs in hOBs following recombinant human TGF-β 1 treatment and investigating the effect of the altered HDACs on both the proliferation and maturation of hOBs and osteogenic cell lines. As expected from our previous work, exposure to rhTGF-β 1 induced the expression of HDACs (HDAC1, -2, -3, -6). However, to our surprise, rhTGF-β 1 treatment strongly suppressed the expression of HDAC9 during osteogenic differentiation. HDAC9 is reported to suppress osteoclastogenesis; however, little is known about the role of HDAC9 in osteogenesis. Chemical inhibition of HDAC9 with TMP269 increased cell numbers of hOBs, but significantly decreased their osteogenic function (alkaline phosphatase activity and matrix mineralization). In osteogenic cell lines (MG-63, CAL-72 and SAOS-2), the expression of HDAC9 negatively correlates with their proliferation capacity and positively correlates with their osteogenic differentiation potential. Being able to boost osteoclasts while inhibiting osteoblasts makes HDAC9 an interesting therapeutic target to support fracture healing and bone metabolisms.Keywords: primary human osteoblasts (phOBs); transforming growth factor β 1 (TGF-β 1 ); histone deacetylase 9 (HDAC9)

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“…Grb2 has been known to play a positive role in receptor tyrosine kinase signaling [24, 25], and the association of Grb2 and Shc/FAK is upstream to the activation of MAPK, which is an important signaling pathway leading to the proliferation and matrix synthesis of chondrocytes when exposed to periodic mechanical stress [26, 27]. We therefore hypothesized that the effect of Grb2 in mechanical signal transduction in chondrocytes may be related to the stimulation of MAPK pathway.…”

Section: Resultsmentioning

confidence: 99%

Proteomic Analysis Reveals Grb2 as a Key Regulator of Periodic Mechanical Stress Transduction in Chondrocytes

Xu¹,

Zeng²,

Wang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Periodic mechanical stress could significantly promote chondrocyte proliferation and matrix synthesis. However, the mechanisms underlying the ability of chondrocyte detecting and responding to periodic mechanical stimuli have not been well delineated. Methods: Quantitative proteomic analysis was performed to construct the differently expressed proteome profiles of chondrocyte under pressure. Then a combination of Western blot, quantitative real-time PCR, lentiviral vector and histological methods were used to confirm the proteomic results and investigate the mechanoseing mechanism. Results: Growth factor receptor-bound protein 2 (Grb2), a component of integrin adhesome, was found a 1.49-fold increase in dynamic stress group. This process was mediated through integrin β1, leading to increased phosphorylation of focal adhesion kinase (FAK) and extracellular signal–regulated kinase 1/2 (ERK1/2) respectively and then produce the corresponding biological effects. Conclusion: This was the first time to demonstrate Grb2 has such an important role in periodic mechanotransduction, and the proteomic data could facilitate the further investigation of chondrocytes mechanosensing.

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Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway in cultured human chondrocytes

Cited by 61 publications

References 51 publications

Hyaluronan suppresses mechanical stress-induced expression of catabolic enzymes by human chondrocytes via inhibition of IL-1β production and subsequent NF-κB activation

Hyaluronan suppresses mechanical stress-induced expression of catabolic enzymes by human chondrocytes via inhibition of IL-1β production and subsequent NF-κB activation

TGF-β1-Dependent Downregulation of HDAC9 Inhibits Maturation of Human Osteoblasts

Proteomic Analysis Reveals Grb2 as a Key Regulator of Periodic Mechanical Stress Transduction in Chondrocytes

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