Summary

BMP6 promotes the differentiation of synovial DIO2+ stem cells into chondrogenic progenitor cells in synovial chondromatosis, revealing a significant chondrogenic capacity in CDH13+ fibroblasts.

Abstract

Objective

Cartilage repair remains a challenging medical issue with a lack of effective solutions to date. Synovial chondromatosis (SC) is a rare benign tumor caused by synovial metaplasia. A characteristic feature of SC is the synovium's spontaneous ability to form translucent cartilage nodules. Currently, the molecular mechanisms behind spontaneous cartilage formation in vivo are poorly understood. Our study aims to investigate the mechanisms of chondrogenesis in SC and the dynamic changes between cell subpopulations at the cellular level using single-cell sequencing technology.

Methods

Synovial tissue samples from 9 patients with SC and 7 normal synovia as controls were collected. Single-cell RNA sequencing was used to assess cell subpopulations within the synovium. RNA velocity and pseudotime trajectory analyses were employed to infer the differentiation trajectories of disease-related cells.

Results

We identified 10 functionally diverse subpopulations of synovial fibroblasts in both SC and healthy synovial tissues, and outlined their RNA velocity in the SC pathological state. However, compared to the control group, we observed a significant abundance difference in the CDH13+ subpopulation of synovial fibroblasts in SC patients (P<0.05). GO analysis revealed that CDH13+ cells possess a stronger chondrogenic capacity. Pseudotime analysis predicted that CDH13+ fibroblasts originate from DIO2+ cells in the synovium, where BMP6 expression was significantly elevated in the SC group and increased progressively with differentiation. Thus, BMP6 can be considered a potential regulatory factor in this emergence.

Conclusion

BMP6 promote the differentiation of synovial DIO2+ stem cells into chondrogenic progenitor cells.