RRC ID 52568
著者 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 CJ.
タイトル Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post-traumatic osteoarthritis.
ジャーナル J Cell Physiol
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.
巻・号 233(8)
ページ 6135-6147
公開日 2018-8-1
DOI 10.1002/jcp.26460
PMID 29323710
MeSH Animals Cartilage Diseases / metabolism Cartilage, Articular / metabolism Cell Differentiation / physiology Cell Line Cell Proliferation / physiology Disease Models, Animal Male Matrix Metalloproteinase 13 / metabolism Menisci, Tibial / metabolism Mice Mice, Inbred C57BL NF-kappa B / metabolism Osteoarthritis / metabolism* Phosphatidylinositol 3-Kinases / metabolism* Proto-Oncogene Proteins c-akt / metabolism* Sclerosis / metabolism* Signal Transduction / physiology* Tibia / metabolism*
IF 4.522
引用数 19
リソース情報
ヒト・動物細胞 ATDC5(RCB0565)