title: Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury.
abstract: Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment. Wnt signals deplete the reservoir of FCSCs and cause cartilage degeneration. We also show that intra-articular treatment with the Wnt inhibitor sclerostin sustains the FCSC pool and regenerates cartilage in a TMJ injury model. We demonstrate the promise of exploiting resident FCSCs as a regenerative therapeutic strategy to substitute cell transplantation that could be beneficial for patients suffering from fibrocartilage injury and disease. These data prompt the examination of utilizing this strategy for other musculoskeletal tissues.
authors.affiliation: TMJ Biology and Regenerative Medicine Laboratory, College of Dental Medicine, Columbia University Medical Center, 630 W 168th St, P&S 16-440, New York, New York 10032, USA.
authors.forename: Mildred C
authors.initials: MC
authors.lastname: Embree
authors.affiliation: Center for Craniofacial Regeneration, College of Dental Medicine, Columbia University Medical Center, 622 W 168th St, New York, New York 10032, USA.
authors.forename: Mo
authors.initials: M
authors.lastname: Chen
authors.affiliation: TMJ Biology and Regenerative Medicine Laboratory, College of Dental Medicine, Columbia University Medical Center, 630 W 168th St, P&S 16-440, New York, New York 10032, USA.
authors.forename: Serhiy
authors.initials: S
authors.lastname: Pylawka
authors.affiliation: Center for Craniofacial Regeneration, College of Dental Medicine, Columbia University Medical Center, 622 W 168th St, New York, New York 10032, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Kong
authors.affiliation: Center for Craniofacial Regeneration, College of Dental Medicine, Columbia University Medical Center, 622 W 168th St, New York, New York 10032, USA.
authors.forename: George M
authors.initials: GM
authors.lastname: Iwaoka
authors.affiliation: Department of Reconstructive Sciences, MC3705, L7005, University of Connecticut Health Sciences Center, 263 Farmington Avenue, Farmington, Connecticut 06032, USA.
authors.forename: Ivo
authors.initials: I
authors.lastname: Kalajzic
authors.affiliation: Clemson-MUSC Bioengineering Program, Department of Bioengineering, Clemson University, 173 Ashley Avenue, MSC 508, Charleston, South Carolina 29425, USA.
authors.forename: Hai
authors.initials: H
authors.lastname: Yao
authors.affiliation: Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, 266 Fangzheng Avenue, Shuitu Hi-tech Industrial Park, Beibei District, Chongqing 400714, China.
authors.forename: Chancheng
authors.initials: C
authors.lastname: Shi
authors.affiliation: W.M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, 604 Allison Road, D-251, Piscataway, New Jersey 08854, USA.
authors.forename: Dongming
authors.initials: D
authors.lastname: Sun
authors.affiliation: Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, New York 14620, USA.
authors.forename: Tzong-Jen
authors.initials: TJ
authors.lastname: Sheu
authors.affiliation: Metropolitan Oral Surgery Associates, 488 Madison Avenue, #200, New York, New York 10022, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Koslovsky
authors.affiliation: College of Dental Medicine, Division of Oral and Maxillofacial Surgery, Columbia University Medical Center, 622 W 168th St, New York, New York 10032, USA.
authors.forename: Alia
authors.initials: A
authors.lastname: Koch
authors.affiliation: Center for Craniofacial Regeneration, College of Dental Medicine, Columbia University Medical Center, 622 W 168th St, New York, New York 10032, USA.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Mao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001842:Bone and Bones / Q000473:pathology; D002454:Cell Differentiation; D019902:Chondrocytes / Q000473:pathology; D051445:Fibrocartilage / Q000166:cytology*; D006023:Glycoproteins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008819:Mice, Nude; D008954:Models, Biological; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D055153:Stem Cell Niche; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013704:Temporomandibular Joint / Q000473:pathology* / Q000503:physiopathology*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D014945:Wound Healing
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C486030:Sost protein, mouse; D051153:Wnt Proteins