Abstract
SummaryThe 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.
Highlights
Skeletal movement is facilitated by synovial joints comprising articular cartilage encased in a capsule
We show that Col22a1 is expressed by Lgr5+ interzone cells prior to the cavitation process, supporting a lineage progression from Lgr5+ interzone cells to Lgr5+/ Col22a1+ double-positive cells as committed progenitors for Col22a1+ juvenile chondrocytes at the articular surface
Lgr5 as a Novel Marker for Distinct Cells in Developing Synovial Joints As interzone cells are progenitor cells, we screened these cells with a panel of stem cell markers and detected Lgr5
Summary
Skeletal movement is facilitated by synovial joints comprising articular cartilage encased in a capsule. Tissue repair involves the recruitment/activation of local progenitor cells, often recapitulating cellular differentiation similar to embryonic development. Studies using Gdf5-Cre (Koyama et al, 2008; Rountree et al, 2004) and inducible Gdf5-CreERT2 mice (Decker et al, 2017; Shwartz et al, 2016) confirmed Gdf5expressing cells contribute to the formation of articular chondrocytes and other joint-related cells. Regional localization of Gdf5+ cells (central or peripheral) in the interzone may influence differentiation of joint cell lineages (Decker et al, 2017). The origin, timing, and location of interzone cells may determine cell fate in the joint tissues
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
