GDF5 reduces MMP13 expression in human chondrocytes via DKK1 mediated canonical Wnt signaling inhibition

Enochson, Lars; Stenberg, Johan; Brittberg, Mats; Lindahl, Anders

doi:10.1016/j.joca.2014.02.004

Cited by 81 publications

(89 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…32 IL-6 can contribute directly to the inhibitory effect of aggrecan via the Notch receptor and thus activate matrix metallopeptidase-13 (MMP-13), a catabolic factor for proteoglycans and type II collagen degradation. [33][34][35][36] In contrast to MMP-13, the tissue metallopeptidase inhibitor-1 (TIMP-1) is an endogenous inhibitor of bone matrix degradation that binds tightly to active MMP-13 and thereby downregulates its activity. 37 In this study, MMP-13, TIMP-1, and IL-6 gene expression were largely unaffected (the latter was only upregulated at 120 psi of cyclic loading) (Figures 3(b) and (4)), indicating no obvious ECM degradation or inflammation at cyclic loading <120 psi and suggesting that cyclic compression has a lesser effect on OA stimulation, as demonstrated by the qPCR and GAG analysis results (Figures 2(b) and 6).…”

Section: Discussionmentioning

confidence: 99%

A novel compressive stress-based osteoarthritis-like chondrocyte system

Young

Chuang

Gefen

et al. 2017

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

The lack of an effective treatment for osteoarthritis (OA) reflects the great need for alternative therapies and drug discovery. Disease models can be used for earlystage compound screening and disease studies. Chondrocytes are solely responsible for the maintenance of the articular cartilage extracellular matrix. Our strategy involved the generation of a cell-based model of OA, a more readily studied disease. Instead of using animal cartilage explants, we incorporated isolated porcine chondrocytes with hydrogel to form threedimensional assemblies. We could identify the specific magnitude-dependent metabolic responses of chondrocytes by applying a series of static and cyclic compression, and therefore successfully generated a novel OA-like cell-based model for drug screening. AbstractMechanical stress damage and insufficient self-repair can contribute to osteoarthritis (OA) in the affected joint. As the effects of stress on chondrocyte metabolism can regulate cartilage homeostasis, the specific stress-response condition is therefore a key to the generation of an OA disease model. We aimed to produce a specific stress-and cell-based OA model after evaluating the metabolic responses of chondrocytes in response to a series of static and cyclic compression stressors. A static load exceeding 40 psi initiated extracellular matrix (ECM) degradation through a decrease in the sulphated-glycosaminoglycan (GAG) content, upregulation of catabolic matrix metalloproteinase (MMP)-13 encoding gene expression, and downregulation of the ECM-related aggrecan and type II collagen encoding genes within 24 h. Indicators of pro-inflammatory events and oxidative stress were found to correlate with increased IL-6 expression and reactive oxygen species (ROS) production, respectively. However, chondrocytes stimulated by moderate cyclic loading (30-40 psi) exhibited increased ECM-related gene expression without significant changes in catabolic and pro-inflammatory gene expression. BMP-7 expression increased at cyclic loading levels above 30-60 psi. These results demonstrated that static compression exceeding 60 psi is sufficient to produce OA-like chondrocytes that exhibit signs of ECM degradation and inflammation. These OA-like chondrocytes could therefore be used as a novel cell-based drug screening system.

show abstract

Section: Discussionmentioning

confidence: 99%

A novel compressive stress-based osteoarthritis-like chondrocyte system

Young

Chuang

Gefen

et al. 2017

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…Similar to TGFβ, BMPs engage serine/threonine kinase receptors that phosphorylate Smad1/5/8, which governs target gene expression. A recent study showed that BMP-14 inhibits MMP-13 expression in chondrocytes 21 . In our previous work, we have shown significantly increased TGFβ 22 and BMP 23 signaling in rotator cuff muscles after massive tendon tears, suggesting TGFβ/BMP signaling may be involved in rotator cuff muscle fatty degeneration through regulating MMP-13 expression.…”

Section: Discussionmentioning

confidence: 99%

Knocking-out matrix metalloproteinase-13 exacerbates rotator cuff muscle fatty infiltration

Liu

Ravishankar

Ning

et al. 2017

MLTJ

View full text Add to dashboard Cite

SummaryIntroduction: Rotator cuff (RC) tears are common tendon injuries. Clinically, both muscle atrophy and fatty infiltration have generally been attributed to poor functional outcomes. Matrix metalloproteinase-13 plays a crucial role in extracellular matrix remodeling in many physiological and pathological processes. Nevertheless, its role in rotator cuff muscle atrophy and fatty infiltration remains unknown. The purpose of this study is to define the functional role of MMP-13 in rotator cuff muscle atrophy and fatty infiltration using a mouse RC tears model. Materials and methods: Unilateral complete supraspinatus and infraspinatus tendon transection and suprascapular nerve transection was performed on nine of MMP-13 (-/-) knockout and nine of MMP-13 (+/+) wildtype mice at 3 months old. Mice were sacrificed 6 weeks after surgery. Supraspinatus (SS) and infraspinatus (IS) muscles were harvested for histology and gene expression analysis with RT-PCR. Results: Six weeks after RC surgery, no significant difference in muscle atrophy and fibrosis between MMP-13 knockout and wild type mice was observed. However, there was a significant increase in the amount of fatty infiltration in MMP-13 knockout mice compared to the wild types. Muscles from MMP-13 knockout mice have significantly higher expression of fatty infiltration related genes.

show abstract

“…In recent years, minimally invasive surgery has been successfully used on the resection of spinal tumors, and the results, when compared with standard open approaches, demonstrated reduced soft tissue destruction (muscle atrophy and denervation), blood loss, and length of hospitalization [17][18][19][20]. Tredway et al published their study including a series of six patents with intradural tumors and demonstrated that minimally invasive approaches are safe and effective with comparable resection and complication rates when compared to historical control.…”

Section: Discussionmentioning

confidence: 99%

“…Tredway et al published their study including a series of six patents with intradural tumors and demonstrated that minimally invasive approaches are safe and effective with comparable resection and complication rates when compared to historical control. However, the data about the suitability of this approach for extradural or intradural-extradural tumors was rare so far [19]. A study published in 2011 by Haji et al highlighted the minimally invasive technique with expandable tubular was carried out for the treatment of extradural, intradural-extramedullary, and intramedullary spinal tumors [17].…”

Section: Discussionmentioning

confidence: 99%

Minimally invasive resection of extradural dumbbell tumors of thoracic spine: surgical techniques and literature review

Ye²,

et al. 2016

Eur Spine J

View full text Add to dashboard Cite

show abstract

GDF5 reduces MMP13 expression in human chondrocytes via DKK1 mediated canonical Wnt signaling inhibition

Abstract: Herein, we provide evidence of a previously unknown link between GDF5 signaling and canonical Wnt signaling that may contribute to the understanding of the molecular mechanisms of OA.

Cited by 81 publications

References 40 publications

A novel compressive stress-based osteoarthritis-like chondrocyte system

A novel compressive stress-based osteoarthritis-like chondrocyte system

Knocking-out matrix metalloproteinase-13 exacerbates rotator cuff muscle fatty infiltration

Minimally invasive resection of extradural dumbbell tumors of thoracic spine: surgical techniques and literature review

Contact Info

Product

Resources

About