title: Extracellular matrix protein 1, a direct targeting molecule of parathyroid hormone-related peptide, negatively regulates chondrogenesis and endochondral ossification via associating with progranulin growth factor.
abstract: Chondrogenesis and endochondral ossification are precisely controlled by cellular interactions with surrounding matrix proteins and growth factors that mediate cellular signaling pathways. Here, we report that extracellular matrix protein 1 (ECM1) is a previously unrecognized regulator of chondrogenesis. ECM1 is induced in the course of chondrogenesis and its expression in chondrocytes strictly depends on parathyroid hormone-related peptide (PTHrP) signaling pathway. Overexpression of ECM1 suppresses, whereas suppression of ECM1 enhances, chondrocyte differentiation and hypertrophy in vitro and ex vivo In addition, target transgene of ECM1 in chondrocytes or osteoblasts in mice leads to striking defects in cartilage development and endochondral bone formation. Of importance, ECM1 seems to be critical for PTHrP action in chondrogenesis, as blockage of ECM1 nearly abolishes PTHrP regulation of chondrocyte hypertrophy, and overexpression of ECM1 rescues disorganized growth plates of PTHrP-null mice. Furthermore, ECM1 and progranulin chondrogenic growth factor constitute an interaction network and act in concert in the regulation of chondrogenesis.-Kong, L., Zhao, Y.-P., Tian, Q.-Y., Feng, J.-Q., Kobayashi, T., Merregaert, J., Liu, C.-J. Extracellular matrix protein 1, a direct targeting molecule of parathyroid hormone-related peptide, negatively regulates chondrogenesis and endochondral ossification via associating with progranulin growth factor.
authors.affiliation: Department of Orthopedic Surgery, New York University School of Medicine, New York, New York, USA;
authors.forename: Li
authors.initials: L
authors.lastname: Kong
authors.affiliation: Department of Orthopedic Surgery, New York University School of Medicine, New York, New York, USA;
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Zhao
authors.affiliation: Department of Orthopedic Surgery, New York University School of Medicine, New York, New York, USA;
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Tian
authors.affiliation: Department of Biomedical Sciences, Texas A&M Baylor College of Dentistry, Dallas, Texas, USA;
authors.forename: Jian-Quan
authors.initials: JQ
authors.lastname: Feng
authors.affiliation: Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA;
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Molecular Biotechnology, University of Antwerp, Antwerp, Belgium;
authors.forename: Joseph
authors.initials: J
authors.lastname: Merregaert
authors.affiliation: Department of Orthopedic Surgery, New York University School of Medicine, New York, New York, USA; Department of Cell Biology, New York University School of Medicine, New York, New York, USA chuanju.liu@med.nyu.edu.
authors.forename: Chuan-Ju
authors.initials: CJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D020219:Chondrogenesis / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D000077155:Granulins; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008822:Mice, Transgenic; D010012:Osteogenesis / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism*; D000077153:Progranulins
chemical_list: C094556:Ecm1 protein, mouse; D016326:Extracellular Matrix Proteins; D000077155:Granulins; C120204:Grn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D044162:Parathyroid Hormone-Related Protein; D000077153:Progranulins
keywords: ECM1; PGRN; PTHrP