The expression of chondrogenesis-related and arthritis-related genes in human ONFH cartilage with different Ficat stages

Gaoyang Chen; Lei Zhong; Qingyu Wang; Zhaoyan Li; Jing Shang; Qiwei Yang; Zhenwu Du; Jincheng Wang; Yang Song; Guizhen Zhang

doi:10.7717/peerj.6306

The expression of chondrogenesis-related and arthritis-related genes in human ONFH cartilage with different Ficat stages

PeerJ. 2019 Jan 16:7:e6306. doi: 10.7717/peerj.6306. eCollection 2019.

Authors

Gaoyang Chen^{1

2

3}, Lei Zhong¹, Qingyu Wang^{1

2

3}, Zhaoyan Li^{1

2

3}, Jing Shang¹, Qiwei Yang^{2

3}, Zhenwu Du^{1

2

3}, Jincheng Wang^{1

3}, Yang Song^{1

3}, Guizhen Zhang^{1

2

3}

Affiliations

¹ Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin, China.
² Research Centre, Second Hospital of Jilin University, Changchun, Jilin, China.
³ The Engineering Research Centre of Molecular Diagnosis and Cell Treatment for Metabolic Bone Diseases of Jilin Province, Changchun, Jilin, China.

Abstract

Background: It has been well known that the degeneration of hip articular cartilage with osteonecrosis of the femoral head (ONFH) increases the instability of hip and accelerates the development process of ONFH. A better understanding of the expression of chondrogenesis-related and arthritis-related genes of cartilage along with the progression of ONFH seems to be essential for further insight into the molecular mechanisms of ONFH pathogenesis.

Methods: We analyzed the differentially expressed gene profile (GSE74089) of human hip articular cartilage with ONFH. The functions and pathway enrichments of differentially expressed genes (DEGs) were analyzed via GO and KEGG analysis. The expression of six selected critical chondrogenesis-related and four arthritis-related genes in eight human hip articular cartilage with femoral neck fracture (FNF) and 26 human hip articular cartilage with different stages ONFH (6 cases of Ficat stage II, 10 cases of Ficat stage III and 10 cases of Ficat stage IV) were detected.

Results: A total of 2,174 DEGs, including 1,482 up-regulated and 692 down-regulated ones, were obtained in the ONFH cartilage specimens compared to the control group. The GO and KEGG enrichment analysis indicated that the function of these DEGs mainly enriched in extracellular matrix, angiogenesis, antigen processing and presentation. The results showed a significant stepwise up-expression of chondrogenesis-related genes, including MMP13, ASPN, COL1A1, OGN, COL2A1 and BMP2, along with the progression of ONFH. The arthritis-related genes IL1β, IL6 and TNFα were only found up-expressed in Ficat IV stage which indicated that the arthritis-related molecular changes were not significant in the progression of ONFH before Ficat III stage. However, the arthritis-related gene PTGS2 was significant stepwise up-expression along with the progression of ONFH which makes it to be a sensitive arthritis-related biomarker of ONFH.

Conclusion: Expression changes of six chondrogenesis-related and four arthritis-related genes were found in hip articular cartilage specimens with different ONFH Ficat stages. These findings are expected to a get a further insight into the molecular mechanisms of ONFH progression.

Keywords: Cartilage; Different ficat stages; Gene expression; ONFH.

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81702195), the Project of Application Demonstration Center of Precision Medicine for Molecular Diagnosis in Jilin Province (2016-2018, NDRC), the Department of Science and Technology of Jilin Province, China (Grant No. 20180520125JH), the Project of Education Department of Jilin Province, China (Grant No. JJKH20170853KJ), the Project of Bethune Youth Foundation of Jilin University, China (Grant No. 2015409), and the Project of Health Management Department of Jilin Province, China (Grant No. 20132003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.