WNT Signalling in Osteoarthritis and Its Pharmacological Targeting

Palma, Armando M. De; Nalesso, Giovanna

doi:10.1007/164_2021_525

Cited by 13 publications

(10 citation statements)

References 99 publications

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“…Its signal transduction involves 19 Wnt genes and various Wnt receptors that regulate the canonical β-catenin-dependent signaling pathway ( Wang et al, 2019 ). The overactivation of the Wnt/β-catenin signaling pathway is related to the degradation process of OA ( Huang et al, 2020 ; Palma and Nalesso, 2021 ). Wang et al (2017) investigated the effects of adiponectin on osteogenic differentiation and bone formation of bone mesenchymal stem cells (BMSCs).…”

Section: Adipokine Signaling Pathways In Osteoarthritismentioning

confidence: 99%

Adipokine Signaling Pathways in Osteoarthritis

Zhang

Lin

Yan

et al. 2022

Front. Bioeng. Biotechnol.

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Osteoarthritis (OA) is a debilitating joint disease that affects millions of individuals. The pathogenesis of OA has not been fully elucidated. Obesity is a well-recognized risk factor for OA. Multiple studies have demonstrated adipokines play a key role in obesity-induced OA. Increasing evidence show that various adipokines may significantly affect the development or clinical course of OA by regulating the pro/anti-inflammatory and anabolic/catabolic balance, matrix remodeling, chondrocyte apoptosis and autophagy, and subchondral bone sclerosis. Several signaling pathways are involved but still have not been systematically investigated. In this article, we review the cellular and molecular mechanisms of adipokines in OA, and highlight the possible signaling pathways. The review suggested adipokines play important roles in obesity-induced OA, and exert downstream function via the activation of various signaling pathways. In addition, some pharmaceuticals targeting these pathways have been applied into ongoing clinical trials and showed encouraging results. However, these signaling pathways are complex and converge into a common network with each other. In the future work, more research is warranted to further investigate how this network works. Moreover, more high quality randomised controlled trials are needed in order to investigate the therapeutic effects of pharmaceuticals against these pathways for the treatment of OA. This review may help researchers to better understand the pathogenesis of OA, so as to provide new insight for future clinical practices and translational research.

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Section: Adipokine Signaling Pathways In Osteoarthritismentioning

confidence: 99%

Adipokine Signaling Pathways in Osteoarthritis

Zhang

Lin

Yan

et al. 2022

Front. Bioeng. Biotechnol.

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“…Several intracellular mechanisms have been shown to be key in maintaining the right threshold of activation of the different branches of the Wnt signalling network. 71,72 Some of these have been reviewed recently by us and others in other reviews [73][74][75][76] and will also be discussed in future publications.…”

Section: Discussionmentioning

confidence: 99%

Wnt signalling in the articular cartilage: A matter of balance

Gill

McCormick

Sochart

et al. 2023

Int J Experimental Path

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Degradation of the articular cartilage is a hallmark of osteoarthritis, a progressive and chronic musculoskeletal condition, affecting millions of people worldwide. The activation of several signalling cascades is altered during disease development: among them, the Wnt signalling plays a pivotal role in the maintenance of tissue homeostasis. Increasing evidence is showing that its activation needs to be maintained within a certain range to avoid the triggering of degenerative mechanisms. In this review, we summarise our current knowledge about how a balanced activation of the Wnt signalling is maintained in the articular cartilage, with a particular focus on receptor‐mediated mechanisms.

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“…The over-stimulation of this pathway contributes to the development of OA. When the Wnt/β-catenin signaling is activated in articular cartilage, it will cause chondrocytes to secrete cartilage catabolic factor MMP13 and other proteins, resulting in OA [39]. TGF-β is a synthetic cytokine, which promotes the proliferation of early chondrocytes and down-regulates the expression of MMPs in chondrocytes by inhibiting the overdifferentiation of end-stage chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

PP2 alleviates the progression of osteoarthritis by inhibiting Wnt/β-catenin and activating TGF- β/Smad signaling

Zhang

Chen

et al. 2023

Preprint

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Objective Explore the effect and mechanism of Src inhibitor PP2 on knee osteoarthritis. Methods The protein expressions of Src, p-Src (y418) and p-FAK in normal and OA human chondrocytes were detected by immunofluorescence (IF). Chondrocytes from the femur and tibial plateau of 3-day-old mice were extracted and inoculated into 6-well plates. The chondrocytes were co-cultured with IL-1β and different doses of PP2, and then the degeneration of chondrocytes was observed. The OA model was induced by destabilizing medial meniscectomy in the right knee of mice; two weeks after the operation, different doses of PP2 were injected intraperitoneally. The medicine was given 3 times a week for 6 weeks, and then we took the knee cartilage of each group, and the degree of degeneration was observed. Results The levels of Src, p-Src (y418) and p-FAK in knee cartilage tissue of patients with OA were abnormally increased. After chondrocytes were co-treated with IL-1β and different doses of PP2, the results showed that PP2 could reduce the abnormal increase of β-catenin, p-β-catenin and other proteins created by IL-1β and reverse the decrease of p-Smad3, Aggrecan and collagen Ⅱ proteins. Meanwhile, intraperitoneal injection of PP2 in vivo significantly reduced the degeneration of articular cartilage. Conclusion Our data show that PP2 can inhibit Wnt/β-catenin and activate TGF-β/Smad signaling, thus protecting the cartilage of OA mice.

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WNT Signalling in Osteoarthritis and Its Pharmacological Targeting

Cited by 13 publications

References 99 publications

Adipokine Signaling Pathways in Osteoarthritis

Adipokine Signaling Pathways in Osteoarthritis

Wnt signalling in the articular cartilage: A matter of balance

PP2 alleviates the progression of osteoarthritis by inhibiting Wnt/β-catenin and activating TGF- β/Smad signaling

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