Universität zu Köln

Heilig, Juliane, Paulsson, Mats and Zaucke, Frank (2016). Insulin-like growth factor 1 receptor (IGF1R) signaling regulates osterix expression and cartilage matrix mineralization during endochondral ossification. Bone, 83. S. 48 - 58. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1873-2763

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Abstract

Insulin-like growth factor I receptor (IGF1R) signaling is important for bone formation via endochondral ossification. Igf1r deficient mice show proportional dwarfism and alterations in chondrocyte proliferation, hypertrophy and apoptosis within the growth plate. In addition, gene ablation in mouse demonstrated that IGF1R signaling is important for osteoblast mediated bone mineralization. However, the mineralization in the terminal hypertrophic zone of the growth plate is also an essential step in endochondral ossification preceding bone formation. Therefore, we analyzed the influence of IGF1R signaling on this process by using mice with a specific deletion of Igf1r in chondrocytes. Studies in embryonic metatarsal explant cultures showed that mineralization of the terminal hypertrophic zone was strongly reduced when IGF1R signaling was lacking. This decreased mineralization may in part result from the delay in hypertrophic differentiation in the Igf1r deficient metatarsals. However, mineralization was impaired even stronger than hypertrophy, suggesting a mineralization promoting effect of IGF signaling that is independent of hypertrophic differentiation. We found a markedly decreased osterix expression suggesting that osterix is a downstream target of IGF1R in chondrocytes. MMP13 expression was strongly reduced in metatarsals lacking the IGF1R while alkaline phosphatase expression and activity were less affected. We conclude that endogenous IGF1R signaling is important for growth plate matrix remodeling and calcification leading to bone formation and suggest that regulation of osterix expression and its downstream target MMP13 are part of the underlying mechanism. (c) 2015 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Heilig, Juliane UNSPECIFIED UNSPECIFIED UNSPECIFIED Paulsson, Mats UNSPECIFIED UNSPECIFIED UNSPECIFIED Zaucke, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-286115
DOI:	10.1016/j.bone.2015.10.007
Journal or Publication Title:	Bone
Volume:	83
Page Range:	S. 48 - 58
Date:	2016
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1873-2763
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FACTOR-I; ALKALINE-PHOSPHATASE; TGF-BETA; CONDITIONAL DELETION; PLATE CHONDROCYTES; BONE; OSTEOBLASTS; COLLAGEN; HORMONE; CELLS Multiple languages Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28611