Depiction of cell atlas and analysis of microenvironment alterations in human meniscus degeneration using single-cell transcriptomic

Background

Musculoskeletal tissue degeneration impairs the life quality and function of many people. Meniscus degeneration is a major origin of knee osteoarthritis and a common threat to athletic ability, but its cellular mechanism remains elusive.

Methods

We built a cell atlas of healthy/degenerated human meniscus using scRNA-seq to investigate meniscal microenvironment homeostasis and its changes in the degeneration process and verified findings with immunofluorescent imaging.

Results

We identified and localized cell types in inner and outer meniscus, found new chondrocyte subtypes contributing to degeneration, and revealed how cellular compositions, functions, and interactions participated in degeneration.

We found that ECM disassembly, angiogenesis, and inflammation form a positive feedback loop driving the degeneration. Comparison of cellular interactions between different degenerative states identified each cell type’s functions in the loop.

Conclusions

The study revealed changes in the meniscal microenvironment during degeneration and discovered new cell subtypes as potential therapeutic targets. The observed mechanism could also be a general model for other joint degenerations.

Funding

The National Natural Science Foundation of China (81972123, 82172508, 62050178, 61721003) and the National Key Research and Development Program of China (2021YFF1200901).