title: Cytokine-like 1 knock-out mice (Cytl1-/-) show normal cartilage and bone development but exhibit augmented osteoarthritic cartilage destruction.
abstract: We have shown that cytokine-like 1 (Cytl1) is a novel autocrine regulatory factor that regulates chondrogenesis of mouse mesenchymal cells (Kim, J. S., Ryoo, Z. Y., and Chun, J. S. (2007) J. Biol. Chem. 282, 29359-29367). In this previous work, we found that Cytl1 expression was very low in mesenchymal cells, increased dramatically during chondrogenesis, and decreased during hypertrophic maturation, both in vivo and in vitro. Moreover, exogenous addition or ectopic expression of Cytl1 caused chondrogenic differentiation of mouse limb bud mesenchymal cells. In the current study, we generated a Cytl1 knock-out (Cytl1(-/-)) mouse to investigate the in vivo role of Cytl1. Deletion of the Cytl1 gene did not affect chondrogenesis or cartilage development. Cytl1(-/-) mice also showed normal endochondral ossification and long bone development. Additionally, ultrastructural features of articular cartilage, such as matrix organization and chondrocyte morphology, were similar in wild-type and Cytl1(-/-) mice. However, Cytl1(-/-) mice were more sensitive to osteoarthritic (OA) cartilage destruction. Compared with wild-type littermates, Cytl1(-/-) mice showed more severe OA cartilage destruction upon destabilization of the medial meniscus of mouse knee joints. In addition, expression levels of Cytl1 were markedly decreased in OA cartilage of humans and experimental mice. Taken together, our results suggest that, rather than regulating cartilage and bone development, Cytl1 is required for the maintenance of cartilage homeostasis, and loss of Cytl1 function is associated with experimental OA cartilage destruction in mice.
authors.affiliation: Cell Dynamics Research Center and School of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
authors.forename: Jimin
authors.initials: J
authors.lastname: Jeon
authors.forename: Hwanhee
authors.initials: H
authors.lastname: Oh
authors.forename: Gyusuk
authors.initials: G
authors.lastname: Lee
authors.forename: Je-Hwang
authors.initials: JH
authors.lastname: Ryu
authors.forename: Jinseol
authors.initials: J
authors.lastname: Rhee
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Kyung-Hwun
authors.initials: KH
authors.lastname: Chung
authors.forename: Woo-Keun
authors.initials: WK
authors.lastname: Song
authors.forename: Churl-Hong
authors.initials: CH
authors.lastname: Chun
authors.forename: Jang-Soo
authors.initials: JS
authors.lastname: Chun
mesh_terms: D000818:Animals; D001483:Base Sequence; D001846:Bone Development / Q000502:physiology*; D002358:Cartilage, Articular / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D002478:Cells, Cultured; D017931:DNA Primers; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D010003:Osteoarthritis / Q000473:pathology*; D018121:Receptors, Cytokine / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D018121:Receptors, Cytokine; C113554:cytokine-like factor-1