Single-Cell RNA Sequencing Reveals Transcriptional Changes in the Cartilage of Subchondral Insufficiency Fracture of the Knee

Abstract

Subchondral insufficiency fracture of the knee (SIFK) is a common cause of knee joint pain that mainly afflicts the elderly. Until now, how a sudden insufficiency fracture of subchondral bone affects the transcriptomic profiles of cartilage in SIFK and OA patients are largely unknown. Methods: Single-cell RNA sequencing (scRNA-seq) was used to identify various cell subsets and evaluate transcriptomic differences in cartilage of SIFK and OA patients. In addition, the above findings were confirmed by histological evaluation and immunohistochemical (IHC) staining. Results: We found that the transcriptomic profiles of cartilage in the SIFK patient was completely different from those of normal and OA patients. Accordingly, several novel cell clusters with activation of hypoxia and endochondral ossification signaling were identified in the SIFK cartilage. Chondrocyte trajectories analysis and IHC staining revealed that transcription factors including TCF4 were found to be highly up-regulated during the occurrence of SIFK, which might drive the reactive formation of cartilage and fibrous tissue and the activation of endochondral ossification. Conclusion: This is the first report to elucidate the transcriptomic alterations and distinct cell type subpopulations in the cartilage of SIFK and OA by the use of scRNA-seq, which provides a new insight in the understanding of the initiation and progression of SIFK.

Single-cell RNA sequencing analysis of the temporomandibular joint condyle in 3 and 4-month-old human embryos

“…Single-cell RNA sequencing has shown that different subpopulations of synovial fibroblasts exist in patients with rheumatoid arthritis (RA) [ 8 ]. Single-cell RNA sequencing revealed the transcriptomic changes in subchondral bone hypoplasia of the knee and in cartilage after traumatic fracture [ 9 ]. Single-cell RNA sequencing has also identified transcriptome heterogeneity and early molecular changes associated with post-traumatic osteoarthritis in mouse articular chondrocytes [ 10 ].…”