From cells to clinic: Single-cell transcriptomics shaping the future of orthopedics

Abstract

Single-cell RNA sequencing (scRNA-seq) technology hold significant potential for advancing orthopedic research. This review examines the impact of ScRNA-seq on the future development of orthopedic research and practice. In the study of osteoarthritis, scRNA-seq can finely characterize the changes in the subsets of chondrocytes and their role in disease progression. In rheumatoid arthritis, this technique reveals the complex heterogeneity and cell-to-cell interactions between fibroblasts and immune cells. ScRNA-seq offers insights into the heterogeneity of nucleus pulposus, annulus fibrosus, and endplate cells, providing a novel perspective on the pathological mechanisms of intervertebral disc degeneration. Single-cell analysis in osteosarcoma research has uncovered the complexity of the tumor microenvironment and mechanisms of immunosuppression. Through these studies, scRNA-seq enhances insights into disease pathogenesis and offers innoviate approaches for precision medicine and personalized treatment strategies.

The translational potential of this article: This article systematically reviews the cellular heterogeneity, molecular mechanisms and immune microenvironment of orthopedic diseases (such as osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, osteosarcoma) by single-cell RNA sequencing (scRNA-seq), which provides a theoretical basis for accurate diagnosis, new therapeutic target discovery (such as TRPV1, CXCR4) and individualized treatment strategies. The combination of multi-omics and spatial transcriptome technology is expected to accelerate clinical translation and optimize the diagnosis and treatment system of orthopedic diseases.

Keywords: Intervertebral disc degeneration; Orthopedic; Osteoarthritis; Osteosarcoma; Rheumatoid arthritis; Single-cell RNA sequencing.

Graphical abstract

Fig. 1

Cellular heterogeneity between OA patients and non-OA controls. (A) The cell fraction difference between patients with OA and non-OA controls. (B) The MIF expressed by other chondrocytes interacts with the CD74-CXCR2/4-CD44 complex expressed by InfCs and activates the MAPK signalling pathway, which increases the expression of the activator protein 1 (AP-1) transcription factor and further promotes the transcription of pro-inflammatory cytokines. (C) An integrative analysis of scRNA-seq data and bulk RNA-seq data demonstrates two major subtypes of patients with OA are stratified by preFC, resulting in an inflammatory-related subtype and a non-inflammatory-related subtype of OA. (D) An integrative analysis of scRNA-seq data and GWAS summary data shows that HTC is the key chondrocyte population that drives the susceptibility to the pathogenesis of OA. Reproduced from Fan Y et al. (2024) with permission from Annals of the Rheumatic Diseases.[15]

Fig. 2

Interaction of synovial fibroblasts with various types of immune cells. Adapted from Cheng et al. (2021) with permission from Front Immunol, with modifications for clarity [101].

Fig. 3

Heterogeneity and intercellular crosstalk in intervertebral disc degeneration. Adapted from Wang et al. (2023) with permission from iScience, with modifications for clarity [102].

Fig. 4

Overview of the crosstalk network between clusters in osteosarcoma [103].