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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\u201013, which was found expressed mainly by osteoblastic cells in subchondral bone. However, this MMP\u201013 induction was attenuated by LY294002 treatment. Furthermore, PI3K\/AKT signaling was found to enhance preosteoblast proliferation, differentiation, and expression of MMP\u201013 by activating NF\u2010\u03baB pathway. In conclusion, inhibition of PI3K\/AKT\/NF\u2010\u03baB axis was able to prevent aberrant bone formation and attenuate cartilage degeneration in OA mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.26460","type":"journal-article","created":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T12:11:43Z","timestamp":1515672703000},"page":"6135-6147","source":"Crossref","is-referenced-by-count":87,"title":["Blocking PI3K\/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post\u2010traumatic osteoarthritis"],"prefix":"10.1002","volume":"233","author":[{"given":"Chuangxin","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Orthopedics The Third Affiliated Hospital of Southern Medical University Guangzhou Guangdong China"},{"name":"Academy of Orthopaedics of Guangdong Province Guangzhou Guangdong China"},{"name":"Orthopaedic Hospital of Guangdong Province Guangzhou Guangdong 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