Joint morphogenetic cells in the adult mammalian synovium

Abstract

The stem cells that safeguard synovial joints in adulthood are undefined. Studies on mesenchymal stromal/stem cells (MSCs) have mainly focused on bone marrow. Here we show that lineage tracing of Gdf5-expressing joint interzone cells identifies in adult mouse synovium an MSC population largely negative for the skeletal stem cell markers Nestin-GFP, Leptin receptor and Gremlin1. Following cartilage injury, Gdf5-lineage cells underpin synovial hyperplasia through proliferation, are recruited to a Nestin-GFPhigh perivascular population, and contribute to cartilage repair. The transcriptional co-factor Yap is upregulated after injury, and its conditional ablation in Gdf5-lineage cells prevents synovial lining hyperplasia and decreases contribution of Gdf5-lineage cells to cartilage repair. Cultured Gdf5-lineage cells exhibit progenitor activity for stable chondrocytes and are able to self-organize three-dimensionally to form a synovial lining-like layer. Finally, human synovial MSCs transduced with Bmp7 display morphogenetic properties by patterning a joint-like organ in vivo. Our findings further the understanding of the skeletal stem/progenitor cells in adult life.

Drug-induced modulation of gp130 signalling prevents articular cartilage degeneration and promotes repair

“…Chondrocyte cloning has been well documented in the past, but this is typically associated with later stages of disease progression;2 RCGD 423 significantly increased rates of EdU incorporation, and it will be critical in future work to determine the molecular identity of these cells as well as to address the relative contributions of proliferation versus anticatabolic effects to the reduction in cartilage degeneration supported by RCGD 423. Moreover, given the decrease in proliferation elicited by the compound at 6 weeks postinjury, it will be important to ascertain if cells capable of responding are limited in the number of divisions they can undergo as this would suggest that other cell types such as synovium43 may need to be harnessed for cartilage repair or that a therapeutic window exists for potential intervention.…”

PTH decreasesin vitrohuman cartilage regeneration without affecting hypertrophic differentiation

“…While at a gene expression level there are similarities in the spatial architecture of growth plate and articular cartilage (43), their embryonic origin is distinctly different. Articular chondrocytes are embryonically derived from the interzone cells forming both the synovial lining and the articular cartilage of the joint (44) and in postnatal stages can be distinguished from growth plate chondrocytes by lubricin expression (45). Possibly, the signaling mechanisms are also different between articular and growth plate chondrocytes.…”

Inflammatory Cytokines Stabilize SOXC Transcription Factors to Mediate the Transformation of Fibroblast‐Like Synoviocytes in Arthritic Disease

“…It is known that FLS are not highly proliferative in adulthood. Only a small proportion of the FLS is known to undergo an extremely slow rate of proliferation, similar to that of stem‐like cells . Moreover, it has also been shown that cell proliferation does not play a significant role in TNF‐induced FLS transformation .…”