Graduate Thesis Or Dissertation
 

Molecular characterization of Wnt/beta-catenin signaling in early equine osteochondrosis

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Molecular characterization of Wnt/β-catenin signaling in early equine osteochondrosis

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/hh63sz345

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  • The objective of this study was to elucidate the expression of signaling molecules associated with the Wnt signaling pathway in cartilage of prepubescent foals and determine their association with chondrocytes located at the osteochondral junction and cartilage canals. Our hypothesis was that increased expression of the components of the Wnt signaling pathway in chondrocytes of the osteochondral junction and cartilage canals would be found in early osteochondrosis (OC) lesions when compared to normal controls. Chondrocytes surrounding cartilage canals and the osteochondral junction were captured using laser capture microdissection from cartilage samples collected from 6 foals with early OC and 8 normal controls. Equine-specific β-catenin, Wnt-4, Wnt-5b, Wnt-11, Dkk-1, Lrp4, Lrp6, Axin1, WIF-1, Sfrp1, Sfrp3, Sfrp5, RARgamma, SC-PEP and 18S mRNA expression levels were evaluated by two-step real-time quantitative PCR. Spatial tissue protein expression of β-catenin, Wnt-11, Wnt 4, and Dkk1 was determined by immunohistochemistry. There was significantly decreased Wnt-11 and increased β-catenin, Wnt-5b, Dkk1, Lrp6, WIF-1, Axin1, and SC-PEP gene expression in early OC chondrocytes along the cartilage canals compared to controls. There was also significantly increased β-catenin and SC-PEP gene expression in early OC chondrocytes along the osteochondral junction compared to normal controls. Wnt 11 showed significantly decreased protein expression in the superficial cartilage layer and Dkk1 showed significantly decreased protein expression in the deep cartilage. Increased gene expression of β-catenin, Wnt 5b, WIF-1, SC-PEP, Axin1, Dkk1, and Lrp6 provides evidence that canonical Wnt signaling is altered in early osteochondrosis of horses and may be associated with disease pathogenesis.
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