{"doi":"10.1016/j.stem.2023.08.004","title":"Lgr5-expressing secretory cells form a Wnt inhibitory niche in cartilage critical for chondrocyte identity","abstract":"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.","journal":"Cell stem cell","year":2023,"id":321482,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":822587,"name":"Peng Chen","orcid":"0000-0002-3069-9997","position":1,"is_corresponding":false},{"id":1033583,"name":"Ikue Tosa","orcid":"0000-0002-2649-661X","position":2,"is_corresponding":false},{"id":634677,"name":"Ziyi Wang","orcid":"0000-0003-1884-8053","position":3,"is_corresponding":false},{"id":463537,"name":"Gan Zhou","orcid":"0000-0002-0379-5086","position":4,"is_corresponding":false},{"id":402809,"name":"Ingrid Safina","orcid":"0000-0003-1036-1101","position":5,"is_corresponding":false},{"id":1033584,"name":"Ran Wei","orcid":"0000-0002-7320-5571","position":6,"is_corresponding":false},{"id":485818,"name":"Mallory M. Morel","orcid":null,"position":7,"is_corresponding":false},{"id":662463,"name":"Alia Koch","orcid":null,"position":8,"is_corresponding":false},{"id":422616,"name":"Michael Forman","orcid":"0000-0003-1238-3072","position":9,"is_corresponding":false},{"id":485819,"name":"Gwendolyn Reeve","orcid":null,"position":10,"is_corresponding":false},{"id":485820,"name":"Michael K. Lecholop","orcid":null,"position":11,"is_corresponding":false},{"id":1034090,"name":"Marshall Wilson","orcid":null,"position":12,"is_corresponding":false},{"id":406569,"name":"Daniel J. Bonthius","orcid":"0000-0001-8927-0661","position":13,"is_corresponding":false},{"id":334118,"name":"Mo Chen","orcid":"0000-0002-6647-8483","position":14,"is_corresponding":false},{"id":1034091,"name":"Mitsuaki Ono","orcid":null,"position":15,"is_corresponding":false},{"id":68288,"name":"Timothy C. Wang","orcid":"0000-0001-5730-3019","position":16,"is_corresponding":false},{"id":228508,"name":"Hai Yao","orcid":"0000-0001-5130-5128","position":17,"is_corresponding":false},{"id":485042,"name":"Mildred C. Embree","orcid":"0000-0003-2256-0001","position":18,"is_corresponding":false},{"id":485817,"name":"Angela Ruscitto","orcid":null,"position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T01:07:32.611759Z","pmid":"37683603","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}