Profile of Matrix-Remodeling Proteinases in Osteoarthritis: Impact of Fibronectin

Pérez‐García, Selene; Carrión, Mar; Gutiérrez‐Cañas, Irene; Villanueva‐Romero, Raúl; Castro, David Martín; Martı́nez, Carmen; González‐Álvaro, Isidoro; Blanco, Francisco J.; Juarranz, Yasmina; Gomariz, Rosa P.

doi:10.3390/cells9010040

Cited by 54 publications

(43 citation statements)

References 203 publications

(359 reference statements)

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“…Under normal circadian rhythm, chondrocytes keep the circadian rhythm stable, and the expression of rhythm-related proteins is normal, which can regulate the dynamic balance between “resting cartilage repair” and “exercise cartilage wear” ( Pérez-García et al., 2019 ). However, under the condition of osteoarthritis, the matrix balance is destroyed, which leads to the gradual loss of cartilage matrix, the clonal expansion of cells, and finally leads to the apoptosis of chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

Circadian Rhythm Protein Bmal1 Modulates Cartilage Gene Expression in Temporomandibular Joint Osteoarthritis via the MAPK/ERK Pathway

Chen

Zhao

et al. 2020

Front. Pharmacol.

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The purpose of this study was to elucidate the role of the circadian gene Bmal1 in human cartilage and its crosstalk with the MAPK/ERK signaling pathway in temporomandibular joint osteoarthritis (TMJ-OA). We verified the periodical variation of the circadian gene Bmal1 and then established a modified multiple platform method (MMPM) to induce circadian rhythm disturbance leading to TMJ-OA. IL-6, pERK , and Bmal1 mRNA and protein expression levels were assessed by real-time RT-PCR and immunohistochemistry. Chondrocytes were treated with an ERK inhibitor (U0126), siRNA and plasmid targeting Bmal1 under IL-6 simulation; then, the cells were subjected to Western blotting to analyze the relationship between Bmal1 and the MAPK/ERK pathway. We found that sleep rhythm disturbance can downregulate the circadian gene BMAL-1 and improve phosphorylated ERK (p-ERK) and IL-6 levels. Furthermore, Bmal1 siRNA transfection was sufficient to improve the pERK level and aggravate OA-like gene expression changes under IL-6 stimulation. Bmal1 overexpression relieved the alterations induced by IL-6, which was consistent with the effect of U0126 (an ERK inhibitor). However, we also found that BMAL1 upregulation can decrease ERK phosphorylation, whereas ERK downregulation did not change BMAL1 expression. Collectively, this study provides new insight into the regulatory mechanism that links chondrocyte BMAL1 to cartilage maintenance and repair in TMJ-OA via the MAPK/ERK pathway and suggests that circadian rhythm disruption is a risk factor for TMJ-OA.

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Section: Introductionmentioning

confidence: 99%

Circadian Rhythm Protein Bmal1 Modulates Cartilage Gene Expression in Temporomandibular Joint Osteoarthritis via the MAPK/ERK Pathway

Chen

Zhao

et al. 2020

Front. Pharmacol.

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“…The root cause of OA is the degeneration of articular cartilage, which is directly caused by the dynamic balance disruption of chondrocytes and extracellular matrix (ECM), that is, the reduction of chondrocytes and faster degradation of extracellular matrix (ECM). Therefore, damaging the function and survival of chondrocytes and promoting the degradation of ECM could lead to articular cartilage damages [1][2]. To investigate the function of miR-146a-5p /TRAF6 in OA chondrocytes and its mechanism, we constructed an OA model of primary chondrocytes with 100 ng/mL SDF-1 in vitro.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR-146a-5p alleviate SDF1-induced cartilage degradation through repression TRAF6 mediated p38-MAPK signal pathway

Wang¹,

Yang²,

Xiang³

et al. 2020

Preprint

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Background : Previous study have revealed that miR-146a-5p has a role in osteoarthritis (OA) development, here, we aim to further explore the underlying mechanism of miR-146a-5P in OA both in vitro and in vitro . Methods : RT-PCR was used to detect the level of miR-146a-5p in OA patients. Primary chondrocytes were treated with SDF-1 to induce an OA model in vitro , and an IL-1β mediated OA model in rats were also used. Gain- or loss- of function assays of miR-146a-5p and TRAF6 were conducted to determine their roles in regulating the proliferation, apoptosis and cartilage degradation of chondrocytes. Results : MiR-146a-5p was overexpressed in OA patients while downregulated in SDF-1 treated chondrocytes. Functionally, miR-146a-5p considerably accelerated the proliferation, inhibited apoptosis and limited ECM degradation of SDF-1 induced chondrocytes. However, TRAF6 upregulation had the opposite effects. Moreover, miR-146a-5p also inhibited OA progression in vivo. Mechanistically, miR-146a-5p targeted at the 3’UTR of TRAF6 and relieved TRAF6 mediated p38-MAPK/NF-κB activation. Conclusions : MiR-146a-5p exerted protective effects chondrocytes against SDF-1 or IL-1β induced OA by regulating the proliferation, apoptosis and ECM degradation of chondrocytes by regulating the TRAF6/ p38-MAPK signaling pathway.

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“…The ECM of articular cartilage is mainly composed of type II collagen and proteoglycan. MMP-13 also named as collagenase-3 can speci cally cleave type II collagen triple helix into characteristic ¾ and ¼ fragments [30][31][32]. Besides type II collagen, MMP-13 degrades other types of collagen, such as type IV and IX, and proteoglycan in cartilage ECM as well [33].…”

Section: Discussionmentioning

confidence: 99%

Progenitor Cells Derived From Injured Cartilage Surface Respond to Damage Associated Molecular Patterns

Ding

Zhou

Zhang

et al. 2020

Preprint

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Objective: To elucidate how chondrogenic progenitor cells (CPCs) originated from mechanically injured cartilage surface respond to proinflammatory endogenous damage-associated-molecular-patterns (DAMPs). Design: Passage 1 bovine CPCs and non-CPCs isolated from injured articular cartilage either by blunt impaction or by scratches were treated with mitochondrial DAMPs (MTDs) composed of fMLF and CpG DNA, or HMGB1 (a nuclear DAMP), or IL-1b for 24 hrs. At the end of the experiments, the expression levels of matrix metalloproteinases (MMPs), chemokines, and cytokines that are associated with cartilage degeneration was examined with Western blotting and quantitative PCR. Results: Both HMGB1 and MTDs remarkably up-regulated expression level of pro-MMP-13 protein in CPCs while showed weak effect on non-CPCs. Compared to non-CPCs, CPCs expressed significantly higher baseline mRNA levels of MMP-13, CXCL12, and IL-6. MTDs further increased the expression levels of MMP-13 and IL-6 in CPCs while HMGB1 did not show such effect. When treated with MTDs, CPCs also expressed significantly higher levels of IL-8 mRNA than did non-CPCs. However, compared to non-CPCs, CPCs expressed much lower levels of MMP-3 and active MMP-13 proteins as well as lower mRNA levels of CCL2 and IL-6 in response to IL-1b. Conclusions: CPCs were more sensitive than non-CPCs in response to DAMPs, especially MTDs, to up-regulate expression of MMP-13, IL-6 and -8. When IL-1b was present, CPCs were less responsive than non-CPCs in terms of up-regulating MMP-3, CCL2, and IL-6 expression. The proinflammatory nature of CPCs implied their critical role in the early phase of PTOA development.

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Profile of Matrix-Remodeling Proteinases in Osteoarthritis: Impact of Fibronectin

Cited by 54 publications

References 203 publications

Circadian Rhythm Protein Bmal1 Modulates Cartilage Gene Expression in Temporomandibular Joint Osteoarthritis via the MAPK/ERK Pathway

Circadian Rhythm Protein Bmal1 Modulates Cartilage Gene Expression in Temporomandibular Joint Osteoarthritis via the MAPK/ERK Pathway

Overexpression of miR-146a-5p alleviate SDF1-induced cartilage degradation through repression TRAF6 mediated p38-MAPK signal pathway

Progenitor Cells Derived From Injured Cartilage Surface Respond to Damage Associated Molecular Patterns

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