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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
Author(s) -
Kong Li,
Zhao YunPeng,
Tian QingYun,
Feng JianQuan,
Kobayashi Tatsuya,
Merregaert Joseph,
Liu ChuanJu
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600261r
Subject(s) - chondrogenesis , endochondral ossification , microbiology and biotechnology , chondrocyte , extracellular matrix , chemistry , parathyroid hormone , parathyroid hormone related protein , cartilage , medicine , endocrinology , biology , anatomy , calcium , stem cell
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. FASEB J. 30, 2741‐2754 (2016). www.fasebj.org