Gene expression profiling of the bone trabecula in patients with osteonecrosis of the femoral head by RNA sequencing

Abstract

Early diagnosis and treatment of osteonecrosis of the femoral head (ONFH) is challenging. Bone trabecula play a vital role in the severity and progression of ONFH. In the present study, the investigators used gene expression profiling of bone trabecula to investigate gene alterations in ONFH patients. Osteonecrotic bone trabecula (ONBT) such as necrosis, fibrosis, and lacuna were confirmed by histological examination in the patients. The adjacent ‘normal’ bone trabecula (ANBT) did not show any pathological changes. Gene sequencing data revealed that although ANBT showed no significant histological changes, alteration of mRNA profiling in ANBT was observed, similar to that in ONBT. Our results indicated that the alteration of mRNA profiling in ANBT may cause normal bone tissue to develop into necrotic bone. RNA-seq data indicated that 2,297 differentially abundant mRNAs were found in the ONBT group (1,032 upregulated and 1,265 downregulated) and 1,523 differentially abundant mRNAs in the ANBT group (744 upregulated and 799 downregulated) compared with the healthy control group. Gene ontology (GO) enrichment analysis suggested that fatty acid metabolism and degradation were the main zones enriched with differentially expressed genes (DEG). Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis indicated that peroxisome proliferator-activated receptor γ (PPAR-γ) pathway was the most significantly regulated pathway. Lipocalin-2 (LCN2), an osteoblast-enriched secreted protein, was significantly decreased in ONBT suggesting that downregulation of LCN2 might affect lipid metabolism and lead to hyperlipidemia, and thus promote pathogenesis of ONFH.

Laboratory indices in patients with osteonecrosis of the femoral head: a retrospective comparative study

“…Numerous investigations have demonstrated that hyperlipidemia constitutes a risk factor for ONFH. The risk factors of indicators and hyperlipidemia indicators are examined [ 11 – 13 ]. Studies have demonstrated that individuals with ONFH commonly exhibit inflammatory reactions.…”

Comparative metabolomic analysis of human cancellous bone reveals the critical role of linoleic acid metabolism in femur head necrosis based on GC-MS

“…In addition, phosphatidylcholine metabolism turbulence were detected in FHN rabbit models (Ren et al, 2018). Our previous study also suggested that this disease was related to the disruption of some genes concerning carbohydrate and lipid metabolism (Bai et al, 2019). In addition, previous study also do some endeavors to found out biomarkers for FHN early diagnosis.…”