ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 2567

Gene Expression in Osteonecrosis of the Femoral Head: A Region-matched RNA-sequencing Study

Lucy Eunju Lee1, Seung Hwan Lee2, Miri Kim2, Jieun Kim2, Joo Sung Shim2, Eun Gyel Shin2, Tae Sung Lee2, Hyuck Min Kwon2, Young Han Lee2, Hun-Mu Yang2, Kwan Kyu Park2 and Jason Jungsik Song2, 1Yonsei University, Seoul, South Korea, 2Yonsei University College of Medicine, Seoul, Republic of Korea

Meeting: ACR Convergence 2024

Keywords: bone biology, Gene Expression, glucocorticoids, osteoblast, osteoclast

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Monday, November 18, 2024

Title: Abstracts: Osteoporosis & Metabolic Bone Disease – Basic & Clinical Science

Session Type: Abstract Session

Session Time: 1:00PM-2:30PM

Background/Purpose: Osteonecrosis of the femoral head (ONFH) is linked to diverse risk factors like glucocorticoid use and excessive alcohol consumption. Various cells may influence bone remodeling, intraosseous pressure, and inflammation, leading to insufficient blood supply and bone tissue loss. However, the roles and interactions of bone cells in ONFH’s development and progression are not well studied. We performed bulk RNA-sequencing on ONFH femoral heads and analyzed it with public single-cell RNA-sequencing data to understand each cell type’s function in different ONFH regions.

Methods: Tissue samples were collected from 17 patients with alcohol-induced (N = 5), steroid-induced (N = 8), or idiopathic (N = 4) ONFH in necrotic and sclerotic zones (Figure 1A). Control samples came from the femoral head and neck of patients with hip osteoarthritis (HOA, N = 5) or femoral neck fractures (FNF, N = 2). RNA was extracted for transcriptome analysis via bulk RNA-seq. Analyses included principal component analysis (PCA), differential expression (DE), and gene ontology (GO) enrichment using R packages edgeR, limma, and ClusterProfiler. We also analyzed public single-cell RNA-seq data from alcohol-induced ONFH patients using Seurat, excluding lymphocytes for clarity [1].

Results: We analyzed 37 samples (26 ONFH, 11 controls), identifying differentially expressed genes (DEGs). PCA on 2315 DEGs showed three well-separated groups: necrotic zone, sclerotic zone, and control head tissue (Figure 1B). Among the 2315 DEGs, 658 were differentially expressed in ONFH necrotic zones versus healthy controls, as shown in a normalized expression heatmap (Figure 1C). GO and pathway analysis highlighted two functional gene groups: ‘Biomineral tissue development’ and ‘Lipid transporter activity’ (Figure 1D).

To verify bulk RNA-seq findings and identify responsible cell types, we analyzed public scRNA-seq data on alcohol-induced ONFH, HOA, and FNF. Analyzing 44,296 cells from ~80k total, we identified 51 cell clusters, including chondrocytes, adipocytes, osteoclasts, and osteoblasts (Figure 2A). Group composition in clusters varied (Figure 2B), with cell type-specific markers localized in adjacent clusters (Figure 2C). Relevant cell types from bulk RNA-seq data were examined, showing differential expression in osteoclasts and adipocytes (Figures 3A and 3B). Genes like RPS4Y1, MT-RNR1, PDK4, TNFAIP3, APOE, FOS, TMEM176B, and JUN were differentially expressed in ONFH osteoclasts. Adipocytes in ONFH increased in number, expressing SPP1, COL1A1, APOC1, CSTB, DCN, FABP5, FABP4, JUND, CD63, and TIMP1 more than other cells.

Conclusion: Our results suggest that extracellular matrix biosynthesis and lipid metabolism are key pathways in ONFH pathophysiology. Gene expression changes are differently regulated across anatomical regions and cell types.

References

1. Liao, Z. et al. Single-cell transcriptome analysis reveals aberrant stromal cells and heterogeneous endothelial cells in alcohol-induced osteonecrosis of the femoral head. Commun. Biol. 5, 324 (2022). https://doi.org/10.1038/s42003-022-03271-6

Supporting image 1

Figure 1. RNA-seq experiments using tissue samples from ONFH, HOA, and FNF revealed differential gene expression in distinct bone regions. (A) Classification of ONFH regions on microCT. Tissue samples from ONFH patients were collected in necrotic and sclerotic zones. (B) PCA on 2315 DEGs, separating three groups of tissue samples. (C) Heatmap of 658 DEGs in ONFH necrotic zones versus control femur heads. (D) Significant GO categories from regional DEGs.

Supporting image 2

Figure 2. Public scRNA-seq data on alcohol-induced ONFH, HOA, and FNF exhibited clusters of different cell types. (A) UMAP plot of 51 clusters from 44,269 cells. (B) A bar plot of cell composition in each cluster. (C) Dot plots and feature plots of genes relatively specific to chondrocytes, adipocytes, osteoclasts, and osteoblasts.

Supporting image 3

Figure 3. The top differential features of osteoclasts and adipocytes contain genes related to extracellular matrix biosynthesis and lipid metabolism. (A) Violin plots of DE features between ONFH and controls (HOA and FNF) in osteoclasts (cluster 24). (B) Violin plots of DE features between adipocytes (clusters 48 and 49) and other cell types. All cells in clusters 48 and 49 are ONFH femur heads.


Disclosures: L. Lee: None; S. Lee: None; M. Kim: None; J. Kim: None; J. Shim: None; E. Shin: None; T. Lee: None; H. Kwon: None; Y. Lee: None; H. Yang: None; K. Park: None; J. Song: None.

To cite this abstract in AMA style:

Lee L, Lee S, Kim M, Kim J, Shim J, Shin E, Lee T, Kwon H, Lee Y, Yang H, Park K, Song J. Gene Expression in Osteonecrosis of the Femoral Head: A Region-matched RNA-sequencing Study [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/gene-expression-in-osteonecrosis-of-the-femoral-head-a-region-matched-rna-sequencing-study/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/gene-expression-in-osteonecrosis-of-the-femoral-head-a-region-matched-rna-sequencing-study/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology