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Regulatory Effects and Interactions of the Wnt and OPG-RANKL-RANK Signaling at the Bone-Cartilage Interface in Osteoarthritis

Department of Biochemistry and Environmental Chemistry, University of Medicine, Pharmacy, Sciences and Technology, Tîrgu Mureș, Romania
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(18), 4653; https://doi.org/10.3390/ijms20184653
Received: 12 August 2019 / Revised: 12 September 2019 / Accepted: 18 September 2019 / Published: 19 September 2019
(This article belongs to the Special Issue The Future of Cartilage Repair in Complex Biological Situations)
Cartilage and the bordering subchondral bone form a functionally active regulatory interface with a prominent role in osteoarthritis pathways. The Wnt and the OPG-RANKL-RANK signaling systems, as key mediators, interact in subchondral bone remodeling. Osteoarthritic osteoblasts polarize into two distinct phenotypes: a low secretory and an activated, pro-inflammatory and anti-resorptive subclass producing high quantities of IL-6, PGE2, and osteoprotegerin, but low levels of RANKL, thus acting as putative effectors of subchondral bone sclerosis. Wnt agonists, Wnt5a, Wisp-1 initiate excessive bone remodeling, while Wnt3a and 5a simultaneously cause loss of proteoglycans and phenotype shift in chondrocytes, with decreased expression of COL2A, aggrecan, and Sox-9. Sclerostin, a Wnt antagonist possesses a protective effect for the cartilage, while DKK-1 inhibits VEGF, suspending neoangiogenesis in the subchondral bone. Experimental conditions mimicking abnormal mechanical load, the pro-inflammatory milieu, but also a decreased OPG/RANKL ratio in the cartilage, trigger chondrocyte apoptosis and loss of the matrix via degradative matrix metalloproteinases, like MMP-13 or MMP-9. Hypoxia, an important cofactor exerts a dual role, promoting matrix synthesis via HIF-1α, a Wnt silencer, but turning on HIF-2α that enhances VEGF and MMP-13, along with aberrant collagen expression and extracellular matrix deterioration in the presence of pro-inflammatory cytokines. View Full-Text
Keywords: osteoarthritis; Wnt signaling; bone-cartilage interface osteoarthritis; Wnt signaling; bone-cartilage interface
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MDPI and ACS Style

Kovács, B.; Vajda, E.; Nagy, E.E. Regulatory Effects and Interactions of the Wnt and OPG-RANKL-RANK Signaling at the Bone-Cartilage Interface in Osteoarthritis. Int. J. Mol. Sci. 2019, 20, 4653. https://doi.org/10.3390/ijms20184653

AMA Style

Kovács B, Vajda E, Nagy EE. Regulatory Effects and Interactions of the Wnt and OPG-RANKL-RANK Signaling at the Bone-Cartilage Interface in Osteoarthritis. International Journal of Molecular Sciences. 2019; 20(18):4653. https://doi.org/10.3390/ijms20184653

Chicago/Turabian Style

Kovács, Béla; Vajda, Enikő; Nagy, Előd E. 2019. "Regulatory Effects and Interactions of the Wnt and OPG-RANKL-RANK Signaling at the Bone-Cartilage Interface in Osteoarthritis" Int. J. Mol. Sci. 20, no. 18: 4653. https://doi.org/10.3390/ijms20184653

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Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

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