Lgr5 and Col22a1 Mark Progenitor Cells in the Lineage toward Juvenile Articular Chondrocytes

Summary The synovial joint forms from a pool of progenitor cells in the future region of the joint, the interzone. Expression of Gdf5 and Wnt9a has been used to mark the earliest cellular processes in the formation of the interzone and the progenitor cells. However, lineage specification and progression toward the different tissues of the joint are not well understood. Here, by lineage-tracing studies we identify a population of Lgr5+ interzone cells that contribute to the formation of cruciate ligaments, synovial membrane, and articular chondrocytes of the joint. This finding is supported by single-cell transcriptome analyses. We show that Col22a1, a marker of early articular chondrocytes, is co-expressed with Lgr5+ cells prior to cavitation as an important lineage marker specifying the progression toward articular chondrocytes. Lgr5+ cells contribute to the repair of a joint defect with the re-establishment of a Col22a1-expressing superficial layer.
Graphical Abstract
Highlights • Lgr5 marks multipotent progenitors and onset of lineage divergence in joint formation • Committed articular chondrocyte progenitor cells co-express Lgr5 and Col22a1 • ECM niche of the juvenile articular superficial surface is rich in COLXXII and CILP • Lgr5+ interzone cells contribute to the repair of the superficial zone of joint defects
Chan and colleagues show that Lgr5 marks a subset of progenitor cells in the developing synovial joints, contributing to the formation of ligaments and articular cartilage. Specific to the articular cartilage lineage are committed progenitors co-expressing Lgr5 and Col22a1 that become Col22a1-expressing juvenile articular cartilage chondrocytes. These cells have high capacity in repairing the superficial zone of a joint defect.