WNT signaling and chondrocytes: from cell fate determination to osteoarthritis physiopathology

Sassi, Nadia; Laadhar, Lilia; Allouche, Mohamed; Achek, Asma; Kallel-Sellami, Mariem; Makni, S.; Sellami, Slaheddine

doi:10.3109/10799893.2013.863919

Cited by 54 publications

(28 citation statements)

References 99 publications

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“…The canonical Wnt pathway triggers its signaling within chondrocytes by regulating intracellular level and subcellular localization of β-catenin [23, 24]. As a pivotal factor in the noncanonical Wnt pathway, Wnt5a can also activate canonical β-catenin signaling, which contributes to the therapeutic effect on OA [25].…”

Section: Introductionmentioning

confidence: 99%

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Zhong

Liang

Yao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Current drug therapies for osteoarthritis (OA) are not practical because of the cytotoxicity and severe side-effects associated with most of them. Artemisinin (ART), an antimalarial agent, is well known for its safety and selectivity to kill injured cells. Based on its anti-inflammatory activity and role in the inhibition of OA-associated Wnt/β-catenin signaling pathway, which is crucial in the pathogenesis of OA, we hypothesized that ART might have an effect on OA. Methods: The chondro-protective and antiarthritic effects of ART on interleukin-1-beta (IL-1β)-induced and OA patient-derived chondrocytes were investigated in vitro using cell viability assay, glycosaminoglycan secretion, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blotting. We also used OA model rats constructed by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) in the joints to investigate the effects of ART on OA by gross observation, morphological staining, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ART exhibited potent anti-inflammatory effects by inhibiting the expression of proinflammatory chemokines and cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, and matrix metallopeptidase-13. It also showed favorable chondro-protective effect as evidenced by enhanced cell proliferation and viability, increased glycosaminoglycan deposition, prevention of chondrocyte apoptosis, and degeneration of cartilage. Further, ART inhibited OA progression and cartilage degradation via the Wnt/β-catenin signaling pathway, suggesting that it might serve as a Wnt/β-catenin antagonist to reduce inflammation and prevent cartilage degradation. Conclusion: In conclusion, ART alleviates IL-1β-mediated inflammatory response and OA progression by regulating the Wnt/β-catenin signaling pathway. Thereby, it might be developed as a potential therapeutic agent for OA.

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Section: Introductionmentioning

confidence: 99%

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Zhong

Liang

Yao

et al. 2018

Cell Physiol Biochem

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“…For example, alterations in TGF-β super-family, Wnt/β-catenin, Notch, and Indian Hedgehog (Ihh) pathways have been shown to contribute to OA development and progression by inducing primarily catabolic responses (15–22). Such responses include upregulation of inflammatory mediators that leads to cartilage extracellular matrix (ECM) degradation via increased expression of matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) (23–27).…”

Section: Oa Pathologymentioning

confidence: 99%

Inflammation and epigenetic regulation in osteoarthritis

Shen

Abu‐Amer

O’Keefe

et al. 2016

Connective Tissue Research

181

121

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Osteoarthritis (OA) was once defined as a non-inflammatory arthropathy, but it is now well-recognized that there is a major inflammatory component to this disease. In addition to synovial cells, articular chondrocytes and other cells of diarthrodial joints are also known to express inflammatory mediators. It has been proposed that targeting inflammation pathways could be a promising strategy to treat OA. There have been many reports of cross-talk between inflammation and epigenetic factors in cartilage. Specifically, inflammatory mediators have been shown to regulate levels of enzymes that catalyze changes in DNA methylation and histone structure, as well as alter levels of non-coding RNAs. In addition, expression levels of a number of these epigenetic factors have been shown to be altered in OA, thereby suggesting potential interplay between inflammation and epigenetics in this disease. This review provides information on inflammatory pathways in arthritis and summarizes published research on how epigenetic regulators are affected by inflammation in chondrocytes. Furthermore, we discuss data showing how altered expression of some of these epigenetic factors can induce either catabolic or anti-catabolic effects in response to inflammatory signals. A better understanding of how inflammation affects epigenetic factors in OA may provide us with novel therapeutic strategies to treat this condition.

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“…Wnts (Wingless-type) constitute a large family of 19 secreted glycoproteins involved in the development, growth and homeostasis of different tissues and organs, including joints, bone and cartilage (reviewed in [151–154]). Wnts bind receptors of the Frizzled (FZD) family receptors on the plasma membrane to initiate several distinct cascades classified as either canonical or non-canonical, depending on whether β-catenin is involved.…”

Section: Wnt/β-catenin Pathwaymentioning

confidence: 99%

“…Chondrogenesis is highly dependent upon cell–ECM and cell–cell adhesion interactions and it has been shown that Wnt signaling is necessary either for the maintenance of mature articular cartilage phenotype, which is characterized by extended cell survival and absence of differentiation towards hypertrophy (schematically reported in Table 1) or for the hypertrophic maturation in the process of endochondral ossification (schematically reported in Table 2) (reviewed by [151,152,154]).…”

Section: Wnt/β-catenin Pathwaymentioning

confidence: 99%

Signaling Pathways in Cartilage Repair

Mariani

Pulsatelli

Facchini

2014

IJMS

141

123

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In adult healthy cartilage, chondrocytes are in a quiescent phase characterized by a fine balance between anabolic and catabolic activities. In ageing, degenerative joint diseases and traumatic injuries of cartilage, a loss of homeostatic conditions and an up-regulation of catabolic pathways occur. Since cartilage differentiation and maintenance of homeostasis are finely tuned by a complex network of signaling molecules and biophysical factors, shedding light on these mechanisms appears to be extremely relevant for both the identification of pathogenic key factors, as specific therapeutic targets, and the development of biological approaches for cartilage regeneration. This review will focus on the main signaling pathways that can activate cellular and molecular processes, regulating the functional behavior of cartilage in both physiological and pathological conditions. These networks may be relevant in the crosstalk among joint compartments and increased knowledge in this field may lead to the development of more effective strategies for inducing cartilage repair.

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WNT signaling and chondrocytes: from cell fate determination to osteoarthritis physiopathology

Abstract: Deeper researches may eventually allow scientists to target WNT pathway in order to help develop efficient therapeutic approaches to treat OA.

Cited by 54 publications

References 99 publications

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Inflammation and epigenetic regulation in osteoarthritis

Signaling Pathways in Cartilage Repair

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