title: Enthesis regeneration: a role for Gli1+ progenitor cells.
abstract: The tendon enthesis originates from a specific pool of hedgehog-active Gli1+ progenitor cells that differentiate and produce mineralized fibrocartilage. The current study investigated the regenerative capacity of this cell population by comparing the responses of early postnatal and mature entheses to injury. Lineage tracing studies demonstrated that the original Gli1+ cell population had the capacity to heal immature entheses after injury, but this capacity was lost after the cells differentiated into mature fibrochondrocytes. To further examine the involvement of Gli1+ cells and hedgehog signaling in enthesis healing, Gli1 expression was examined via lineage tracing approaches and the effect of Smo deletion was examined in the injured entheses. Immature injured entheses retained high levels of Gli1 expression, a marker of hedgehog activation, consistent with non-injured controls. In contrast, injured mature entheses had few Gli1+ cells early in the healing process, with limited recovery of the cell population later in the healing process. These results suggest that the presence of activated hedgehog signaling in enthesis cells early in the healing process may enhance healing of enthesis injuries by mimicking developmental processes.
authors.affiliation: Department of Orthopedic Surgery, Washington University, St. Louis, MO 63110, USA.
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Schwartz
authors.affiliation: Department of Orthopedic Surgery, Icahn School of Medicine at Mount Sinai Hospital, Mount Sinai Health System, New York, NY 10029, USA.
authors.forename: Leesa M
authors.initials: LM
authors.lastname: Galatz
authors.affiliation: Department of Orthopedic Surgery, Columbia University, New York, NY 10032, USA sat2@columbia.edu.|Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA.
authors.forename: Stavros
authors.identifier: 0000-0003-1531-4849
authors.initials: S
authors.lastname: Thomopoulos
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D051379:Mice; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*; D013710:Tendons / Q000502:physiology*; D014945:Wound Healing; D000071676:Zinc Finger Protein GLI1 / Q000378:metabolism*
chemical_list: C498520:Gli1 protein, mouse; D000071676:Zinc Finger Protein GLI1
keywords: Enthesis; Fibrocartilage; Hedgehog; Regeneration; Stem cell; Tendon