Regulation of biomechanical signals by NF-κB transcription factors in chondrocytes

Anghelina, Mirela; Sjostrom, Danen; Perera, P.; Nam, Jin; Knobloch, Thomas J.; Agarwal, Sudha

doi:10.3233/bir-2008-0472

Cited by 18 publications

(9 citation statements)

References 71 publications

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“…In the NF-kappa B signaling pathway, lymphotoxin beta ( Ltb ), tumor necrosis factor receptor associated factor 1 ( Traf1 ), vascular cell adhesion molecule 1 ( Vcam1 ), and matrix metallopeptidase ( Mmp )-13 are down-regulated while cartilage specific markers Sox9, Col2a1 and Acan are upregulated by PC compared with P. It has been reported that Ltb is an inducer of the inflammatory response system, which induces the expression of Vcam1 [41] or Traf1 [42] or Mmp13 , [43] contributing to inflammation and prevention of Sox9-based chondrogenesis [44]. Findings from Anghelina et al [45] and Futosi et al [46] support our explanation and suggest that a physiologically low level of mechanical loading has anti-inflammatory effects through the downregulation of Ltb, Traf1, Vcam1 and Mmp13 and simultaneously enhances matrix synthesis ( Acan and Col2a1 ) in the cartilage/chondrocyte microenvironment. Il-17 is reported as a downstream molecule of Traf1 , and both are pro-inflammatory mediators [47].…”

Section: Resultsmentioning

confidence: 99%

Mechanically cartilage-mimicking poly(PCL-PTHF urethane)/collagen nanofibers induce chondrogenesis by blocking NF–kappa B signaling pathway

et al. 2018

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Cartilage cannot self-repair and thus regeneration is a promising approach to its repair. Here we developed new electrospun nanofibers, made of poly (ε-caprolactone)/polytetrahydrofuran (PCL-PTHF urethane) and collagen I from calf skin (termed PC), to trigger the chondrogenic differentiation of mesenchymal stem cells (MSCs) and the cartilage regeneration in vivo. We found that the PC nanofibers had a modulus (4.3 Mpa) lower than the PCL-PTHF urethane nanofibers without collagen I from calf skin (termed P) (6.8 Mpa) although both values are within the range of the modulus of natural cartilage (1-10 MPa). Both P and PC nanofibers did not show obvious difference in the morphology and size. Surprisingly, in the absence of the additional chondrogenesis inducers, the softer PC nanofibers could induce the chondrogenic differentiation in vitro and cartilage regeneration in vivo more efficiently than the stiffer P nanofibers. Using mRNA-sequence analysis, we found that the PC nanofibers outperformed P nanofibers in inducing chondrogenesis by specifically blocking the NF-kappa B signaling pathway to suppress inflammation. Our work shows that the PC nanofibers can serve as building blocks of new scaffolds for cartilage regeneration and provides new insights on the effect of the mechanical properties of the nanofibers on the cartilage regeneration.

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Section: Resultsmentioning

confidence: 99%

Mechanically cartilage-mimicking poly(PCL-PTHF urethane)/collagen nanofibers induce chondrogenesis by blocking NF–kappa B signaling pathway

et al. 2018

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“…The present study documents the effects of GTW as a form of exercise on global gene regulation in the articular cartilage of the knee affected with MIA in various stages. In MIA, acute inflammation and chronic inflammation drive the destruction of the knee, whereas inhibition of matrix synthesis and its breakdown prevent repair, which worsens the joint damage (32–35). We showed that GTW suppresses inflammation and up‐regulates repair to prevent active progression of cartilage damage.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-wide gene regulation by gentle treadmill walking during the progression of monoiodoacetate-induced arthritis

Nam

Perera

Liu

et al. 2011

Arthritis & Rheumatism

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Objective. Physiotherapies are the most widely recommended conservative treatment for arthritic diseases. The present study was undertaken to examine the molecular mechanisms underlying the effects of gentle treadmill walking (GTW) on various stages of monoiodoacetate-induced arthritis (MIA) to elucidate the basis for the success or failure of such therapies in joint damage.Methods. Knees were obtained from untreated control rats, rats with MIA that did not undergo GTW, rats with MIA in which GTW regimens were started 1 day post-MIA induction, and rats with MIA in which GTW regimens were started after cartilage damage had progressed to grade 1 or grade 2. The cartilage was examined macroscopically, microscopically, and by microfocal computed tomography imaging. Transcriptome-wide gene expression analysis was performed, and microarray data were assessed by Ingenuity Pathways Analysis to identify molecular functional networks regulated by GTW.Results. GTW intervention started on day 1 post-MIA induction significantly prevented the progression of MIA, but its efficacy was reduced when implemented on knees exhibiting close to grade 1 cartilage damage.GTW accelerated cartilage damage in knees with close to grade 2 damage. Transcriptome-wide gene expression analysis revealed that GTW intervention started 1 day post-MIA inception significantly suppressed inflammation-associated genes and up-regulated matrixassociated gene networks. However, delayed GTW intervention after grade 1 damage had occurred was less effective in suppressing proinflammatory genes or upregulating matrix synthesis.Conclusion. The present findings suggest that GTW suppresses proinflammatory gene networks and up-regulates matrix synthesis to prevent progression of cartilage damage in MIA-affected knees. However, the extent of cartilage damage at the initiation of GTW may be an important determinant of the success or failure of such therapies.

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“…50 NF-B transcription factors are involved in immune and inflammatory responses and regulate expression of genes responsible for inflammation, apoptosis, cell cycle, and matrix breakdown. 51,52 In response to various stimuli such as TNF-␣, IL-1␤, and lipopolysaccharides (LPS), NF-B is activated and translocates to the nucleus to regulate transcription of its target genes. 53 With treadmill exercise, expression of many genes required for NF-B activity was suppressed, suggesting the suppression of NF-B activation mediates the anti-inflammatory effects of exercise.…”

Section: Chondrocyte Mechanotransductionmentioning

confidence: 99%

“…The NF‐κB network was one of the gene clusters suppressed by treadmill exercise 50 . NF‐κB transcription factors are involved in immune and inflammatory responses and regulate expression of genes responsible for inflammation, apoptosis, cell cycle, and matrix breakdown 51,52 . In response to various stimuli such as TNF‐α, IL‐1β, and lipopolysaccharides (LPS), NF‐κB is activated and translocates to the nucleus to regulate transcription of its target genes 53 .…”

Section: Chondrocyte Mechanotransductionmentioning

confidence: 99%

Mechanotransduction and cartilage integrity

Leong

Hardin²,

Cobelli³

et al. 2011

Annals of the New York Academy of Sciences

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Osteoarthritis (OA) is characterized by the breakdown of articular cartilage that is mediated in part by increased production of matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS), enzymes that degrade components of the cartilage extracellular matrix. Efforts to design synthetic inhibitors of MMPs/ADAMTS have only led to limited clinical success. In addition to pharmacologic therapies, physiologic joint loading is widely recommended as a nonpharmacologic approach to improve joint function in osteoarthritis. Clinical trials report that moderate levels of exercise exert beneficial effects, such as improvements in pain and physical function. Experimental studies demonstrate that mechanical loading mitigates joint destruction through the downregulation of MMPs/ADAMTS. However, the molecular mechanisms underlying these effects of physiologic loading on arthritic joints are not well understood. We review here the recent progress on mechanotransduction in articular joints, highlighting the mediators and pathways in the maintenance of cartilage integrity, especially in the prevention of cartilage degradation in OA.

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Regulation of biomechanical signals by NF-κB transcription factors in chondrocytes

Cited by 18 publications

References 71 publications

Mechanically cartilage-mimicking poly(PCL-PTHF urethane)/collagen nanofibers induce chondrogenesis by blocking NF–kappa B signaling pathway

Mechanically cartilage-mimicking poly(PCL-PTHF urethane)/collagen nanofibers induce chondrogenesis by blocking NF–kappa B signaling pathway

Transcriptome-wide gene regulation by gentle treadmill walking during the progression of monoiodoacetate-induced arthritis

Mechanotransduction and cartilage integrity

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