Cartilage tissue from sites of weight bearing in osteoarthritis patients exhibits a differential phenotype with distinct chondrocytes subests
Description
Background Osteoarthritis (OA) is a degenerative joint disease that is associated with excessive mechanical loading. The aim here was to elucidate whether different subpopulations of chondrocytes exhibit distinct phenotypes in response to variations in loading conditions. Furthermore, we seek to investigate the transcriptional switches and cell crosstalk among these subsets of chondrocytes. Methods Proteomic analysis was performed on cartilage tissue isolated from weight bearing and non-weight bearing regions of the joint. Additionally, single-cell RNA sequencing was used to identify different subsets of chondrocytes, including hypertrophic chondrocytes (HCs) and OA hypertrophic chondrocytes (OAHCs)s. By applying pseudotime and cell communication analyses, it was found that OAHCs exhibit unique transcriptional and cell interaction features that distinguish them from other subpopulations of chondrocytes. These cells were induced to differentiate in vitro through stimulation with TGFβ, and their presence was also confirmed in pathological sections of human OA cartilage tissue. The molecular mechanisms underlying transcriptional changes in these cells were analyzed through whole-transcriptome sequencing. Findings The weight bearing region of OA cartilage tissue harbors a subpopulation of chondrocytes, referred to as OAHCs, which display unique features compared to the hypertrophic chondrocytes present in healthy cartilage. The existence of these specialized cells provides a plausible explanation for the dualistic effects of TGFβ signaling pathway in response to excessive mechanical loading, as observed in both normal and pathologic cartilage tissues. Interpretation Although TGFβ signaling pathway is known to prevent hypesrtrophy and differentiation of chondrocytes in healthy cartilage, the intricate sensitivity of OAHCs in weight-bearing cartilage to this pathway leads to their hypertrophic differentiation and the development of OA phenotype, even upon minimal stimulation by active TGFβ.
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Institutions
- Third Affiliated Hospital of Sun Yat-Sen University
- Sun Yat-Sen University