{"doi":"10.1101/2022.12.09.519810","title":"Wnt-associated adult stem cell marker Lgr6 is required for osteogenesis and fracture healing","abstract":"Abstract Despite the remarkable regenerative capacity of skeletal tissues, nonunion of bone and failure of fractures to heal properly presents a significant clinical concern. Stem and progenitor cells are present in bone and become activated following injury; thus, elucidating mechanisms that promote adult stem cell-mediated healing is important. Wnt-associated adult stem marker Lgr6 is implicated in the regeneration of tissues with well-defined stem cell niches in stem cell-reliant organs. Here, we demonstrate that Lgr6 is dynamically expressed in osteoprogenitors in response to fracture injury. Using an Lgr6- null mouse model, we find that Lgr6 expression is necessary for maintaining bone volume and efficient postnatal bone regeneration in adult mice. Skeletal progenitors isolated from Lgr6-null mice have reduced colony-forming potential and reduced osteogenic differentiation capacity due to attenuated cWnt signaling. Lgr6 -null mice consist of a lower proportion of self-renewing stem cells. In response to fracture injury, Lgr6-null mice have deficient proliferation of periosteal progenitors and reduced ALP activity. Further, analysis of bone regeneration phase and remodeling phase of fracture healing in Lgr6-null mice showed impaired endochondral ossification and reduced mineralization. We propose that in contrast to not being required for successful skeletal development Lgr6-positive cells have a direct role in endochondral bone repair.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":313780,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":377824,"name":"Matthew Wan","orcid":null,"position":1,"is_corresponding":false},{"id":1012834,"name":"Anna Peterson","orcid":null,"position":2,"is_corresponding":false},{"id":40825,"name":"Daniel W. Youngstrom","orcid":"0000-0002-1193-8868","position":3,"is_corresponding":false},{"id":653732,"name":"Justin S. King","orcid":"0000-0002-6469-9872","position":4,"is_corresponding":false},{"id":376762,"name":"Ivo Kalajzić","orcid":"0000-0002-6752-3442","position":5,"is_corresponding":false},{"id":40826,"name":"Kurt D. Hankenson","orcid":"0000-0001-6361-143X","position":6,"is_corresponding":false},{"id":376763,"name":"Archana Sanjay","orcid":"0000-0002-0149-4837","position":7,"is_corresponding":false},{"id":376761,"name":"Laura Doherty","orcid":"0000-0003-3692-7716","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T00:33:48.490749Z","pmid":null,"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":[]}