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. 2023 Oct 17;9(4):e003255. doi: 10.1136/rmdopen-2023-003255

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© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Single-cell sequencing of human knee articular cartilage tissues from weight-bearing and non-weight-bearing regions. (A) The single-cell RNA sequencing (scRNAseq) of chondrocytes was visualised using Uniform Manifold Approximation and Projection (UMAP) plots, which demonstrated 12 distinct chondrocyte subsets. A total of n=3 patients with OA were included in the study, and chondrocytes from both weight-bearing (iMT) and non-weight-bearing (oLT) cartilage patient-matched sites were subjected to scRNAseq analysis. (B) Identification of a disparate population (black circle) in OA cartilage undergoing transitions from non-weight-bearing to weight-bearing states, visualised through UMAP plot split by weight-bearing conditions (oLT vs iMT). (C) UMAP plot illustrates the distribution of chondrocyte subsets under different weight-bearing conditions (upper panel). Percentage distribution of the 12 different subsets according to either weight-bearing (iMT) or non-weight-bearing (oLT) sites (lower panel). (D) Milo analysis reveals a significant upregulation in the abundance of cell neighbourhoods in the disparate subset (black circle) compared with other subpopulations. (E) Heatmap showing the z-score average gene signature expression of the top 5 most differentially expressed genes within each of the 12 chondrocytes clusters.