Flightless I is a catabolic factor of chondrocytes that promotes hypertrophy and cartilage degeneration in osteoarthritis

被引：17

作者：

Ebata, Taku ^{[1
,2
]}

Terkawi, Mohamad Alaa ^{[1
,2
]}

Hamasaki, Masanari ^{[1
,2
]}

Matsumae, Gen ^{[1
,2
]}

Onodera, Tomohiro ^{[1
,2
]}

Aly, Mahmoud Khamis ^{[1
,2
]}

Yokota, Shunichi ^{[1
,2
]}

Alhasan, Hend ^{[1
,2
]}

Shimizu, Tomohiro ^{[1
,2
]}

Takahashi, Daisuke ^{[1
,2
]}

Homan, Kentaro ^{[1
,2
]}

Kadoya, Ken ^{[1
,2
]}

Iwasaki, Norimasa ^{[1
,2
]}

机构：

[1] Hokkaido Univ, Fac Med, Dept Orthoped Surg, Kita Ku, Kita 15,Nish 7, Sapporo, Hokkaido 0608638, Japan

[2] Hokkaido Univ, Grad Sch Med, Kita Ku, Kita 15,Nish 7, Sapporo, Hokkaido 0608638, Japan

来源：

ISCIENCE | 2021年 / 24卷 / 06期

关键词：

REGULATOR; DISEASE; PROTEIN;

D O I：

10.1016/j.isci.2021.102643

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Synovial macrophages that are activated by cartilage fragments initiate synovitis, a condition that promotes hypertrophic changes in chondrocytes leading to cartilage degeneration in OA. In this study, we analyzed the molecular response of chondrocytes under condition of this type of stimulation to identify a molecular therapeutic target. Stimulated macrophages promoted hypertrophic changes in chondrocytes resulting in production of matrix-degrading enzymes of cartilage. Among the top-upregulated genes, FliI was found to be released from activated chondrocytes and exerted autocrine/paracrine effects on chondrocytes leading to an increase in expression of catabolic and hypertrophic factors. Silencing FliI in stimulated cells significantly reduced expression of catabolic and hypertrophic factors in cocultured chondrocytes. Our further results demonstrated that the FliI-TLR4-ERK1/2 axis is involved in the hypertrophic signaling of chondrocytes and catabolism of cartilage. Our findings provide a new insight into the pathogenesis of OA and identify a potentially new molecular target for diagnostics and therapeutics.

引用

页数：17

共 37 条

[1]

Prospects for disease modification in osteoarthritis [J].