Effects of GGCX overexpression on anterior cruciate ligament transection-induced osteoarthritis in rabbits

Fu,Xiaoling; Qiu,Ruiyun; Tang,Chunfang; Wang,Xiaomei; Cheng,Xigao; Yin,Ming

doi:10.3892/mmr.2017.8304

Effects of GGCX overexpression on anterior cruciate ligament transection-induced osteoarthritis in rabbits

Authors:
- Xiaoling Fu
- Ruiyun Qiu
- Chunfang Tang
- Xiaomei Wang
- Xigao Cheng
- Ming Yin
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Affiliations: Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, College of Information Engineering, Nanchang University, Nanchang, Jiangxi 330031, P.R. China, Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Nanchang, Jiangxi 341099, P.R. China
Published online on: December 18, 2017 https://doi.org/10.3892/mmr.2017.8304
Pages: 3821-3828

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Abstract

Effective therapeutic methods for osteoarthritis (OA) are lacking. γ‑glutamyl carboxylase (GGCX) is a key enzyme that regulates carboxylation of cartilage matrix Gla protein (MGP). Whether GGCX overexpression protects against OA remains unknown. The aim of the present study was to explore the effects of GGCX overexpression on anterior cruciate ligament transection (ACLT)‑induced OA and its mechanisms in Japanese white rabbits. ACLT surgery was used to establish an OA model in rabbits. A total of 48 rabbits were randomly divided into 4 groups: Sham, OA model + GGCX overexpression plasmid, OA model + saline and OA model + empty vector. The expression of uncarboxylated MGP (ucMGP), carboxylated MGP (cMGP), matrix metalloproteinase (MMP)‑13, collagen type X, collagen type II, tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β were detected by ELISA, immunohistochemistry, reverse transcription‑quantitative polymerase chain reaction and western blotting. Morphological changes to tibial cartilage were assessed by Giemsa and safranin O‑fast green staining, respectively. Compared with the Sham control, GGCX expression was significantly decreased in the OA Model group. GGCX expression was increased by injection of a lentivirus‑carried overexpression plasmid that encoded GGCX. GGCX overexpression ameliorated ATLC‑induced damage in articular cartilage. OA Model rabbits exhibited significantly decreased expression levels of cMGP and collagen type II, and increased expression of ucMGP, collagen type X, MMP‑13, IL‑1β and TNF‑α. Notably, these expression levels were reversed by GGCX overexpression in OA Model rabbits. Results from the present study indicated that GGCX expression was decreased in OA Model rabbits, whereas overexpression of GGCX was able to promote carboxylation of MGP, reduce inflammation, decrease MMP‑13 expression and regulate collagen expression. The results also indicated that GGCX may serve as a therapeutic target for OA.

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