Histone deacetylase 3 suppresses Erk phosphorylation and matrix metalloproteinase (Mmp)-13 activity in chondrocytes

Carpio, Lomeli R.; Bradley, Elizabeth W.

doi:10.1080/03008207.2016.1236088

Cited by 14 publications

(13 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Runx2 activity can also be blocked by repressors such as HDAC4, which results in inhibition of MMP‐13 promoter activity in osteoblastic cells (Shimizu, Selvamurugan, Westendorf, Olson, & Partridge, ). HDAC3 has also been shown to suppress the phosphorylation of ERK as well as its downstream target Runx2, which results in the inhibition of MMP‐13 activity in chondrocytes (Carpio, Bradley, & Westendorf, ). Hence, Runx2 phosphorylation appears to be an important event that controls bone remodeling by regulating MMP‐13 expression.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of Runx2 phosphorylation sites required for TGF‐β1‐mediated stimulation of matrix metalloproteinase‐13 expression in osteoblastic cells

Arumugam

Vairamani

Partridge

et al. 2017

Journal Cellular Physiology

View full text Add to dashboard Cite

Transforming growth factor-beta1 (TGF-β1), a highly abundant growth factor in skeletal tissues, stimulates matrix metalloproteinase-13 (MMP-13) expression in osteoblastic cells. MMP-13 plays a critical role in bone remodeling. Runx2, a bone transcription factor, is required for TGF-β1-mediated stimulation of MMP-13 expression in osteoblastic cells. In this study, the molecular mechanism responsible for TGF-β1-stimulation of MMP-13 expression via Runx2 in osteoblastic cells was elucidated. TGF-β1 stimulated the phosphorylation of Runx2 at serine amino acids, and ERK inhibition blocked this effect in rat (UMR106-01) and human (MG-63) osteoblastic cells. Pretreatment with okadaic acid, a serine-threonine phosphatase inhibitor, increased Runx2 serine phosphorylation in osteoblastic cells. When cells were pretreated with an ERK inhibitor, TGF-β1-mediated stimulation of MMP-13 mRNA expression decreased. Nano-ESI/LC/MS analysis identified that TGF-β1 stimulates Runx2 phosphorylation at three serine amino acids. Transient transfection of mouse mesenchymal stem cells (C3H10T1/2) with Runx2 serine mutant constructs decreased TGF-β1-mediated Runx2 serine phosphorylation. A luciferase reporter assay identified that TGF-β1 stimulated MMP-13 promoter activity in these cells only in the presence of the wild Runx2 construct, and not with mutant Runx2. Thus, TGF-β1 stimulates the phosphorylation of Runx2 at three serine amino acids, and this event is required for MMP-13 expression in osteoblastic cells. Hence, this study contributes to the knowledge of events governing bone remodeling and bone-related diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

“…HDAC3 has also been shown to suppress the phosphorylation of ERK as well as its downstream target Runx2, which results in the inhibition of MMP-13 activity in chondrocytes (Carpio, Bradley, & Westendorf, 2017). Hence, Runx2 phosphorylation appears to be an important event that controls bone remodeling by regulating MMP-13 expression.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Runx2 phosphorylation sites required for TGF‐β1‐mediated stimulation of matrix metalloproteinase‐13 expression in osteoblastic cells

Arumugam

Vairamani

Partridge

et al. 2017

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Postnatal ablation of HDAC3 in chondrocytes delays chondrocyte endochondral maturation, ossification and induces inflammatory cytokines in normal chondrocytes ( Carpio et al, 2016 ). HDAC3 also inhibits the Erk1/2 downstream proteins (Runx2 and MMP13) and promotes chondrocyte maturation in the growth plate, which inhibits temporal and spatial activation of Erk1/2 through the up-regulation of the dual-specific phosphatase Dusp6 ( Carpio et al, 2017 ). HDAC3 also represses Phlpp1 transcription to promote Akt phosphorylation and activation of its downstream targets (mTOR and p70 SK6) in chondrocytes.…”

Section: Hdacs and Signaling Pathways In Cartilage Development And Oamentioning

confidence: 99%

The Role of HDACs and HDACi in Cartilage and Osteoarthritis

Zhang

Yang

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Epigenetics plays an important role in the pathogenesis and treatment of osteoarthritis (OA). In recent decades, HDAC family members have been associated with OA. This paper aims to describe the different role of HDACs in the pathogenesis of OA through interaction with microRNAs and the regulation of relevant signaling pathways. We found that HDACs are involved in cartilage and chondrocyte development but also play a crucial role in OA. However, the distinct HDAC mechanism in the pathogenesis and treatment of OA require further investigation. Furthermore, HDAC inhibitors (HDACi) can protect cartilage from disease, which may represent a potential therapeutic approach against OA.

show abstract

“…Decreased levels of HDACs 3 and 4 are associated with increased bone catabolism, proposedly mediated via increased expression of FGF-21 and MMPs (e.g., MMP3, MMP10, and MMP13) [196,223,224,225]. Interaction with PTH, often increased during CLD, may alter HDAC4-dependent expression of these genes [225,226,227].…”

Section: Alterations In Transforming Growth Factor-β Superfamily Imentioning

confidence: 99%

Hepatic Osteodystrophy—Molecular Mechanisms Proposed to Favor Its Development

Ehnert¹,

Aspera-Werz²,

Ruoß³

et al. 2019

IJMS

View full text Add to dashboard Cite

Almost all patients with chronic liver diseases (CLD) show altered bone metabolism. Depending on the etiology, this manifests in a severe osteoporosis in up to 75% of the affected patients. Due to high prevalence, the generic term hepatic osteodystrophy (HOD) evolved, describing altered bone metabolism, decreased bone mineral density, and deterioration of bone structure in patients with CLD. Once developed, HOD is difficult to treat and increases the risk of fragility fractures. Existing fractures affect the quality of life and, more importantly, long-term prognosis of these patients, which presents with increased mortality. Thus, special care is required to support the healing process. However, for early diagnosis (reduce fracture risk) and development of adequate treatment strategies (support healing of existing fractures), it is essential to understand the underlying mechanisms that link disturbed liver function with this bone phenotype. In the present review, we summarize proposed molecular mechanisms favoring the development of HOD and compromising the healing of associated fractures, including alterations in vitamin D metabolism and action, disbalances in transforming growth factor beta (TGF-β) and bone morphogenetic protein (BMP) signaling with histone deacetylases (HDACs) as secondary regulators, as well as alterations in the receptor activator of nuclear factor kappa B ligand (RANKL)–osteoprotegerin (OPG) system mediated by sclerostin. Based on these mechanisms, we give an overview on the limitations of early diagnosis of HOD with established serum markers.

show abstract

Histone deacetylase 3 suppresses Erk phosphorylation and matrix metalloproteinase (Mmp)-13 activity in chondrocytes

Cited by 14 publications

References 57 publications

Characterization of Runx2 phosphorylation sites required for TGF‐β1‐mediated stimulation of matrix metalloproteinase‐13 expression in osteoblastic cells

Characterization of Runx2 phosphorylation sites required for TGF‐β1‐mediated stimulation of matrix metalloproteinase‐13 expression in osteoblastic cells

The Role of HDACs and HDACi in Cartilage and Osteoarthritis

Hepatic Osteodystrophy—Molecular Mechanisms Proposed to Favor Its Development

Contact Info

Product

Resources

About