title: Ancient origin of lubricated joints in bony vertebrates.
abstract: Synovial joints are the lubricated connections between the bones of our body that are commonly affected in arthritis. It is assumed that synovial joints first evolved as vertebrates came to land, with ray-finned fishes lacking lubricated joints. Here, we examine the expression and function of a critical lubricating protein of mammalian synovial joints, Prg4/Lubricin, in diverse ray-finned fishes. We find that Prg4 homologs are specifically enriched at the jaw and pectoral fin joints of zebrafish, stickleback, and gar, with genetic deletion of the zebrafish prg4b gene resulting in the same age-related degeneration of joints as seen in lubricin-deficient mice and humans. Our data support lubricated synovial joints evolving much earlier than currently accepted, at least in the common ancestor of all bony vertebrates. Establishment of the first arthritis model in the highly regenerative zebrafish will offer unique opportunities to understand the aetiology and possible treatment of synovial joint disease.
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States.|Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of University of Southern California, Los Angeles, United States.
authors.forename: Amjad
authors.initials: A
authors.lastname: Askary
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States.|Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of University of Southern California, Los Angeles, United States.
authors.forename: Joanna
authors.initials: J
authors.lastname: Smeeton
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States.|Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of University of Southern California, Los Angeles, United States.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Paul
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States.|Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of University of Southern California, Los Angeles, United States.
authors.forename: Simone
authors.initials: S
authors.lastname: Schindler
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, United States.|Department of Integrative Biology and Program in Ecology, Michigan State University, East Lansing, United States.|Department of Evolutionary Biology and Behavior, Michigan State University, East Lansing, United States.
authors.forename: Ingo
authors.initials: I
authors.lastname: Braasch
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Ellis
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, United States.
authors.forename: John
authors.initials: J
authors.lastname: Postlethwait
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
authors.forename: Craig T
authors.initials: CT
authors.lastname: Miller
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States.|Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of University of Southern California, Los Angeles, United States.
authors.forename: J Gage
authors.identifier: 0000-0002-3209-0026
authors.initials: JG
authors.lastname: Crump
mesh_terms: D000818:Animals; D005075:Biological Evolution; D006023:Glycoproteins / Q000235:genetics*; D007596:Joints / Q000502:physiology*; D013582:Synovial Fluid / Q000502:physiology*; D014714:Vertebrates; D000099158:Proteoglycan 4
chemical_list: D006023:Glycoproteins; D000099158:Proteoglycan 4
keywords: articular cartilage; developmental biology; evolutionary biology; genomics; prg4; spotted gar; stem cells; stickleback; synovial joint; zebrafish