title: Distribution of slow-cycling cells in epiphyseal cartilage and requirement of β-catenin signaling for their maintenance in growth plate.
abstract: Slow proliferation is one of the characteristics of stem cells. We examined the presence, distribution, and regulation of slow-cycling cells in the developing and growing skeleton using a pulse-chase method with a new nucleoside derivative, 5-ethynyl-2'-deoxyuridine (EdU). C57BL/6 mice received daily intraperitoneal injections of EdU from postnatal day 4 to day 7. One day after the last EdU injection, a large population of cells in articular cartilage and growth plate was labeled. Six weeks after the last injection, the number of EdU-labeled cells dramatically decreased, but a small number of them were dominantly present in the articular surface, and the labeling index was significantly higher in the surface than that in the rest of articular cartilage. In the growth plate, most EdU-positive cells were found in the top layer that lies immediately below the secondary ossification center. Interestingly, postnatal conditional ablation of β-catenin in cartilage caused a complete loss of the EdU-labeled cells in growth plate that displayed disorganization and dysfunction. Together, our data demonstrate that slow-cycling cells do reside in specific locations and numbers in both articular cartilage and growth plate. The β-catenin signaling pathway appears to play a previously unsuspected role in maintenance of the slow-cycling cells.
authors.affiliation: Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, Department of Surgery, Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, ARC 902, Philadelphia, Pennsylvania, 19104.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Candela
authors.forename: Leslie
authors.initials: L
authors.lastname: Cantley
authors.forename: Rika
authors.initials: R
authors.lastname: Yasuaha
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwamoto
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pacifici
authors.forename: Motomi
authors.initials: M
authors.lastname: Enomoto-Iwamoto
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000378:metabolism; D006132:Growth Plate / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000502:physiology*; D051176:beta Catenin / Q000172:deficiency / Q000502:physiology*
chemical_list: D051176:beta Catenin; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine
keywords: Wnt/β-catenin signaling; cartilage; slow-cycling cells; stem/progenitor cells