CRLF1 Is a Key Regulator in the Ligamentum Flavum Hypertrophy

Frontiers in Cell and Developmental Biology

Tao Jiang¹  Zhenyu Zheng¹  Peng Li¹  Liang Wang¹  Zhengnan Lian¹  Xiang Ao¹  Zhongmin Zhang³ 

[1] Academy of Orthopedics, Guangzhou, China;Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China;Division of Spine Surgery, Department of Orthopadics, Nanfang Hospital, Southern Medical University, Guangzhou, China;

关键词: ligamentum flavum hypertrophy;    CRLF1;    fibrosis;    proteomics analysis;    mouse model;   

DOI  :  10.3389/fcell.2020.00858

来源: DOAJ

【 摘 要 】

Hypertrophy of the ligamentum flavum (HLF) is one of the common causes of lumbar spinal stenosis (LSS). The key molecules and mechanisms responsible for HLF remain unclear. Here, we used an integrated transcriptome and proteomics analysis of human ligamentum flavum (LF), and subsequent immunohistochemistry and real-time PCR assays, to show upregulation of CRLF1 to be the dominant response to HLF. TGF-β1 significantly increased mRNA expression of CRLF1 through SMAD3 pathway. CRLF1 enhanced LF fibrosis via ERK signaling pathway at the post-transcriptional level and was required for the pro-fibrotic effect of TGF-β1. Knockdown of CRLF1 was shown here to reduce fibrosis caused by inflammatory cytokines and mechanical stress. Furthermore, we found that bipedal standing posture can cause HLF and upregulation of CRLF1 expression in mice LF. Overexpression of CRLF1 was indicated to cause HLF in vivo, whereas CRLF1 knockdown impeded the formation of HLF in bipedal standing mice. These results revealed a crucial role of CRLF1 in LF hypertrophy. We propose that inhibition of CRLF1 is a potential therapeutic strategy to treat HLF.

【 授权许可】

Unknown