| First Author | Ruscitto A | Year | 2023 |
| Journal | Cell Stem Cell | Volume | 30 |
| Issue | 9 | Pages | 1179-1198.e7 |
| PubMed ID | 37683603 | Mgi Jnum | J:340421 |
| Mgi Id | MGI:7528579 | Doi | 10.1016/j.stem.2023.08.004 |
| Citation | Ruscitto A, et al. (2023) Lgr5-expressing secretory cells form a Wnt inhibitory niche in cartilage critical for chondrocyte identity. Cell Stem Cell 30(9):1179-1198.e7 |
| abstractText | Osteoarthritis is a degenerative joint disease that causes pain, degradation, and dysfunction. Excessive canonical Wnt signaling in osteoarthritis contributes to chondrocyte phenotypic instability and loss of cartilage homeostasis; however, the regulatory niche is unknown. Using the temporomandibular joint as a model in multiple species, we identify Lgr5-expressing secretory cells as forming a Wnt inhibitory niche that instruct Wnt-inactive chondroprogenitors to form the nascent synovial joint and regulate chondrocyte lineage and identity. Lgr5 ablation or suppression during joint development, aging, or osteoarthritis results in depletion of Wnt-inactive chondroprogenitors and a surge of Wnt-activated, phenotypically unstable chondrocytes with osteoblast-like properties. We recapitulate the cartilage niche and create StemJEL, an injectable hydrogel therapy combining hyaluronic acid and sclerostin. Local delivery of StemJEL to post-traumatic osteoarthritic jaw and knee joints in rabbit, rat, and mini-pig models restores cartilage homeostasis, chondrocyte identity, and joint function. We provide proof of principal that StemJEL preserves the chondrocyte niche and alleviates osteoarthritis. |
