期刊
FEBS OPEN BIO
卷 8, 期 6, 页码 962-973出版社
WILEY
DOI: 10.1002/2211-5463.12438
关键词
angiotensin II type 1 receptor; chondrocyte; G-protein-dependent pathway; hypertrophic differentiation; mechanosensor
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT KAKENHI) [16K10923]
- Grants-in-Aid for Scientific Research [16K10923] Funding Source: KAKEN
Angiotensin II type 1 receptor (AT1R) appears to have a mechanosensing function in a number of cell types. The purpose of this study was to examine whether AT1R expressed in articular chondrocytes is involved in osteoarthritis (OA) progression in vivo and whether cyclic compressive loading activates the AT1R and stimulates hypertrophic differentiation of chondrocytes in vitro. The relationships between the modified Mankin score for cartilage degeneration and the expression of AT1R and type X collagen (Col X) were studied in mouse knees with OA induced using the destabilization-of-medial-meniscus model. Cyclic compressive loads were applied to cultured bovine articular chondrocytes in three-dimensional agarose scaffolds. Expression of Col X and runt-related transcription factor 2 (Runx2) was analyzed using RT-PCR and western blotting. We dissected the downstream pathway for intracellular signal transductions of AT1R including G-protein-dependent and G-protein-independent pathways. Positive significant correlations between the Mankin score and the rate of AT1R-immunopositive cells and between the rates of AT1R and Col X expression were noted. The expression of Col X and Runx2 was increased by compressive loading but suppressed by addition of olmesartan, an Ang II receptor blocker, to the agarose scaffolds. Compressive loading upregulated the phosphorylation of c-Jun N-terminal kinase (JNK), Src, and STAT1, but olmesartan significantly suppressed only JNK phosphorylation. We conclude that AT1R expressed by articular chondrocytes may be involved in OA progression in vivo. Mechanical stress can activate AT1R and stimulate hypertrophic differentiation of chondrocytes through the G-protein-dependent pathway. AT1R has a mechanosensing function in chondrocytes and may be a new therapeutic target in OA.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据