Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/113900
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Type: Journal article
Title: Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post-traumatic osteoarthritis
Author: Lin, C.
Shao, Y.
Zeng, C.
Zhao, C.
Fang, H.
Wang, L.
Pan, J.
Liu, L.
Qi, W.
Feng, X.
Qiu, H.
Zhang, H.
Chen, Y.
Wang, H.
Cai, D.
Xian, C.
Citation: Journal of Cellular Physiology, 2018; 233(8):6135-6147
Publisher: Wiley
Issue Date: 2018
ISSN: 0021-9541
1097-4652
Statement of
Responsibility: 
Chuangxin Lin, Yan Shao, Chun Zeng, Chang Zhao, Hang Fang, Liping Wang, Jianying Pan, Liangliang Liu, Weizhong Qi, Xiaofeng Feng, Hong Qiu, Haiyang Zhang, Yuhui Chen, Hong Wang, Daozhang Cai, Cory J. Xian
Abstract: PI3K/AKT signaling is essential in regulating pathophysiology of osteoarthritis (OA). However, its potential modulatory role in early OA progression has not been investigated yet. Here, a mouse destabilization OA model in the tibia was used to investigate roles of PI3K/AKT signaling in the early subchondral bone changes and OA pathological process. We revealed a significant increase in PI3K/AKT signaling activation which was associated with aberrant bone formation in tibial subchondral bone following destabilizing the medial meniscus (DMM), which was effectively prevented by treatment with PI3K/AKT signaling inhibitor LY294002. PI3K/AKT signaling inhibition attenuated articular cartilage degeneration. Serum and bone biochemical analyses revealed increased levels of MMP-13, which was found expressed mainly by osteoblastic cells in subchondral bone. However, this MMP-13 induction was attenuated by LY294002 treatment. Furthermore, PI3K/AKT signaling was found to enhance preosteoblast proliferation, differentiation, and expression of MMP-13 by activating NF-κB pathway. In conclusion, inhibition of PI3K/AKT/NF-κB axis was able to prevent aberrant bone formation and attenuate cartilage degeneration in OA mice.
Keywords: PI3K/AKT signaling
articular cartilage
osteoarthritis
preosteoblasts
subchondral bone
Rights: © 2018 Wiley Periodicals, Inc.
DOI: 10.1002/jcp.26460
Grant ID: http://purl.org/au-research/grants/nhmrc/1094606
http://purl.org/au-research/grants/nhmrc/1042105
Appears in Collections:Aurora harvest 8
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