title: Superficial cells are self-renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice.
abstract: Articular cartilage has little regenerative capacity. Recently, genetic lineage tracing experiments have revealed chondrocyte progenitors at the articular surface. We further characterized these progenitors by usingin vivogenetic approaches. Histone H2B-green fluorescent protein retention revealed that superficial cells divide more slowly than underlying articular chondrocytes. Clonal genetic tracing combined with immunohistochemistry revealed that superficial cells renew their number by symmetric division, express mesenchymal stem cell markers, and generate chondrocytesviaboth asymmetric and symmetric differentiation. Quantitative analysis of cellular kinetics, in combination with phosphotungstic acid-enhanced micro-computed tomography, showed that superficial cells generate chondrocytes and contribute to the growth and reshaping of articular cartilage. Furthermore, we found that cartilage renewal occurs as the progeny of superficial cells fully replace fetal chondrocytes during early postnatal life. Thus, superficial cells are self-renewing progenitors that are capable of maintaining their own population and fulfilling criteria of unipotent adult stem cells. Furthermore, the progeny of these cells reconstitute adult articular cartilagede novo,entirely substituting fetal chondrocytes.-Li, L., Newton, P. T., Bouderlique, T., Sejnohova, M., Zikmund, T., Kozhemyakina, E., Xie, M., Krivanek, J., Kaiser, J., Qian, H., Dyachuk, V., Lassar, A. B., Warman, M. L., Barenius, B., Adameyko, I., Chagin, A. S. Superficial cells are self-renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Phillip T
authors.initials: PT
authors.lastname: Newton
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Thibault
authors.initials: T
authors.lastname: Bouderlique
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Sejnohova
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Zikmund
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Kozhemyakina
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Meng
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Jan
authors.initials: J
authors.lastname: Krivanek
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
authors.forename: Jozef
authors.initials: J
authors.lastname: Kaiser
authors.affiliation: Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hong
authors.initials: H
authors.lastname: Qian
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Dyachuk
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lassar
authors.affiliation: Orthopedic Research Labs, Boston Children's Hospital, Boston, Massachusetts, USA; and.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Warman
authors.affiliation: Orthopaedic Section, Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Barenius
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.|Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Igor
authors.initials: I
authors.lastname: Adameyko
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; andrei.chagin@ki.se.
authors.forename: Andrei S
authors.initials: AS
authors.lastname: Chagin
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology* / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology*; D020219:Chondrogenesis; D051379:Mice; D012038:Regeneration
keywords: adult stem cells; bone; osteoarthritis; regeneration; superficial zone