Regulation of mechanical stress-induced MMP-13 and ADAMTS-5 expression by RUNX-2 transcriptional factor in SW1353 chondrocyte-like cells

Tetsunaga, Tomonori; Nishida, Keiichiro; Furumatsu, Takayuki; Naruse, Keiji; Hirohata, Satoshi; Yoshida, Aki; Saito, Taichi; Ozaki, T.

doi:10.1016/j.joca.2010.11.004

Cited by 129 publications

(126 citation statements)

References 49 publications

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“…The stress-induced MAPK pathways, including the ERK, c-Jun N-terminal kinase (JNK) and p38 MAPK cascades, coordinate the induction and activation of gene expression through transcription factors such as activator protein 1 (cFos/cJun), ETS, C/EBPβ, and Runx2 [Goldring and Sandell, 2007;Long and Loeser, 2010;Tetsunaga et al 2011;Tsuchimochi et al 2010]. Induction of both ADAMTS4 and 5 requires Runx2 [Tetsunaga et al 2011], and NFκB and HIF2α [Yang et al 2010] mediate ADAMTS4 upregulation, whereas MMP-13 induction requires all three transcription factors. Recent studies indicate that epigenetic mechanisms also play a role through modulation of the DNA methylation status on promoters driving expression of, for example, IL1B and MMP13 genes [Hashimoto et al 2009] or through dysregulation of the microRNAs that are important for maintenance of homeostasis [Dudek et al 2010;Miyaki et al 2010].…”

Section: Inflammation and Mechanical Stress In Osteoarthritismentioning

confidence: 99%

Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis

Goldring

2012

Therapeutic Advances in Musculoskeletal

372

302

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Chondrogenesis occurs as a result of mesenchymal cell condensation and chondroprogenitor cell differentiation. Following chondrogenesis, the chondrocytes remain as resting cells to form the articular cartilage or undergo proliferation, terminal differentiation to chondrocyte hypertrophy, and apoptosis in a process termed endochondral ossification, whereby the hypertrophic cartilage is replaced by bone. Human adult articular cartilage is a complex tissue of matrix proteins that varies from superficial to deep layers and from loaded to unloaded zones. A major challenge to efforts to repair cartilage by stem cell-based and other tissue-engineering strategies is the inability of the resident chondrocytes to lay down a new matrix with the same properties as it had when it was formed during development. Thus, understanding and comparing the mechanisms of cartilage remodeling during development, osteoarthritis (OA), and aging may lead to more effective strategies for preventing cartilage damage and promoting repair. The pivotal proteinase that marks OA progression is matrix metalloproteinase 13 (MMP-13), the major type II collagen-degrading collagenase, which is regulated by both stress and inflammatory signals. We and other investigators have found that there are common mediators of these processes in human OA cartilage. We also observe temporal and spatial expression of these mediators in early through late stages of OA in mouse models and are analyzing the consequences of knockout or transgenic overexpression of critical genes. Since the chondrocytes in adult human cartilage are normally quiescent and maintain the matrix in a low turnover state, understanding how they undergo phenotypic modulation and promote matrix destruction and abnormal repair in OA may to lead to identification of critical targets for therapy to block cartilage damage and promote effective cartilage repair.

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Section: Inflammation and Mechanical Stress In Osteoarthritismentioning

confidence: 99%

Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis

Goldring

2012

Therapeutic Advances in Musculoskeletal

372

302

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“…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%

“…In addition, it has been suggested that inflammatory cytokines such as IL-1b also play an important role in regulating the expression of ADAMTSs or MMPs [22]. In the current study, we used human chondrocytes to examine whether HA affects the mechanical stress-induced gene expression of ADAMTS-4, ADAMTS-5, and MMP-13 in vitro.…”

Section: Introductionmentioning

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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“…Proteoglycan and collagen degradation are principally carried out by members of the matrix metalloproteinase (MMP) family, such as MMP3, MMP7, and MMP13, which play important roles in degrading cartilage collagens [7][8][9]. However, previous biochemical studies have demonstrated that members of the a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family such as ADAMTS-1, -4, -5, -8, -9, and -15 possess aggrecanase activity and can induce the degradation of cartilage proteoglycan-aggrecan in OA [10][11][12][13][14]. Knockdown of ADAMTS-4/5 exerted protective effects against proteoglycan degradation and attenuated the severity of murine OA [15], and the degradation of aggrecan was decreased when ADAMTS-4/5 small interfering RNA was used in human cartilage stimulated by IL-1β [16].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes

Mao¹,

Zhang²,

Zhang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) are secreted enzymes belonging to the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family that play significant roles in the progression of osteoarthritis (OA). Here, we aimed to determine whether the expression of ADAMTS-4/5 in chondrogenesis and inflammation is regulated by microRNA-92a-3p (miR-92a-3p). Methods: MiR-92a-3p and ADAMTS-4/5 expressions were determined by quantitative polymerase chain reaction (qPCR). To investigate the repressive effect of miR-92a-3p on ADAMTS-4/5 expression, chondrogenic human mesenchymal stem cells (hMSCs) and human chondrocytes were transfected with mature miR-92a-3p or an antisense inhibitor (anti-miR-92a-3p), respectively. ADAMTS-4/5 protein production was quantified by enzyme-linked immunosorbent assay (ELISA), and miR92a-3p involvement in IL-1β-mediated catabolic effects was examined by immunoblotting. The roles of activated MAP kinases (MAPK) and nuclear factor (NF)-κB were evaluated by using specific inhibitors. Interaction between miR-92a-3p and its putative binding site in the 3′-untranslated region (3′-UTR) of ADAMTS-4/5 mRNA was confirmed by luciferase reporter assay. Results: miR-92a-3p expression was elevated in chondrogenic hMSCs, with significantly lower expression in OA cartilage than in normal cartilage. Stimulation with IL-1β significantly reduced miR-92a-3p expression in primary human chondrocytes (PHCs). Transfection of chondrocytes with miR-92a-3p downregulated IL-1β-induced ADAMTS-4/5 expression, and the activity of a reporter construct containing the 3′-UTR of human ADAMTS-4/5 mRNA.

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Regulation of mechanical stress-induced MMP-13 and ADAMTS-5 expression by RUNX-2 transcriptional factor in SW1353 chondrocyte-like cells

Abstract: RUNX-2 might have a role as a key downstream mediator of p38's ability to regulate mechanical stress-induced MMP-13 and ADAMTS-5 expression.

Cited by 129 publications

References 49 publications

Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis

Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis

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

MicroRNA-92a-3p Regulates Aggrecanase-1 and Aggrecanase-2 Expression in Chondrogenesis and IL-1β-Induced Catabolism in Human Articular Chondrocytes

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