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Discoidin domain receptor 1 regulates endochondral ossification through terminal differentiation of chondrocytes
Author(s) -
Chou LiangYin,
Chen ChungHwan,
Lin YiHsiung,
Chuang ShuChun,
Chou HsinChiao,
Lin SungYen,
Fu YinChi,
Chang JeKen,
Ho MeiLing,
Wang ChauZen
Publication year - 2020
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.201901852rr
Subject(s) - discoidin domain , endochondral ossification , microbiology and biotechnology , terminal (telecommunication) , ddr1 , chemistry , cartilage , biology , anatomy , signal transduction , computer science , receptor tyrosine kinase , telecommunications
Chondrocytes in growth plates are responsible for longitudinal growth in long bones during endochondral ossification. Discoidin domain receptor 1 ( Ddr1 ) is expressed in chondrocytes, but the molecular mechanisms by which DDR1 regulates chondrocyte behaviors during the endochondral ossification process remain undefined. To elucidate Ddr1 ‐mediate chondrocyte functions, we generated chondrocyte‐specific Ddr1 knockout (CKOΔ Ddr1 ) mice in this study. The CKOΔ Ddr1 mice showed delayed development of the secondary ossification center and increased growth plate length in the hind limbs. In the tibial growth plate in CKOΔ Ddr1 mice, chondrocyte proliferation was reduced in the proliferation zone, and remarkable downregulation of Ihh, MMP13, and Col‐X expression in chondrocytes resulted in decreased terminal differentiation in the hypertrophic zone. Furthermore, apoptotic chondrocytes were reduced in the growth plates of CKOΔ Ddr1 mice. We concluded that chondrocytes with Ddr1 knockout exhibit decreased proliferation, terminal differentiation, and apoptosis in growth plates, which delays endochondral ossification and results in short stature. We also demonstrated that Ddr1 regulates the Ihh/Gli1/Gli2/Col‐X pathway to regulate chondrocyte terminal differentiation. These results indicate that Ddr1 is required for chondrocytes to regulate endochondral ossification in skeletal development.