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The Local CNP/GC-B system in growth plate is responsible for physiological endochondral bone growth.

ABSTRACT: Recent studies revealed C-type natriuretic peptide (CNP) and its receptor, guanylyl cyclase-B (GC-B) are potent stimulators of endochondral bone growth. As they exist ubiquitously in body, we investigated the physiological role of the local CNP/GC-B in the growth plate on bone growth using cartilage-specific knockout mice. Bones were severely shorter in cartilage-specific CNP or GC-B knockout mice and the extent was almost the same as that in respective systemic knockout mice. Cartilage-specific GC-B knockout mice were shorter than cartilage-specific CNP knockout mice. Hypertrophic chondrocyte layer of the growth plate was drastically reduced and proliferative chondrocyte layer, along with the proliferation of chondrocytes there, was moderately reduced in either cartilage-specific knockout mice. The survival rate of cartilage-specific CNP knockout mice was comparable to that of systemic CNP knockout mice. The local CNP/GC-B system in growth plate is responsible for physiological endochondral bone growth and might further affect mortality via unknown mechanisms.

SUBMITTER: Nakao K

PROVIDER: S-EPMC5395013 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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The Local CNP/GC-B system in growth plate is responsible for physiological endochondral bone growth.

Nakao Kazumasa K Osawa Kenji K Yasoda Akihiro A Yamanaka Shigeki S Fujii Toshihito T Kondo Eri E Koyama Noriaki N Kanamoto Naotetsu N Miura Masako M Kuwahara Koichiro K Akiyama Haruhiko H Bessho Kazuhisa K Nakao Kazuwa K

Scientific reports 20150527

Recent studies revealed C-type natriuretic peptide (CNP) and its receptor, guanylyl cyclase-B (GC-B) are potent stimulators of endochondral bone growth. As they exist ubiquitously in body, we investigated the physiological role of the local CNP/GC-B in the growth plate on bone growth using cartilage-specific knockout mice. Bones were severely shorter in cartilage-specific CNP or GC-B knockout mice and the extent was almost the same as that in respective systemic knockout mice. Cartilage-specific ...[more]

PMID: 26014585

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Project description:A variety of cell cultures models and in vivo approaches have been used to study gene expression during chondrocyte differentiation. The extent to which the in vitro models reflect bona fide gene regulation in the growth plate has not been quantified. In addition, studies that evaluate global gene expression changes among different growth plate zones are limited. To address these issues, we completed a microarray screen of three growth plate zones derived from manually segmented embryonic mouse tibiae. Classification of genes differentially expressed between each respective growth plate zone, functional categorization as well as characterization of gene expression patterns, cytogenetic loci, signaling pathways and functional motifs confirmed documented data and pointed to novel aspects of chondrocyte differentiation. Parallel comparisons of the microdissected tibiae data set to our previously completed micromass culture screen further corroborated the suitability of micromass cultures for modeling gene expression in chondrocyte development. The micromass culture system demonstrated striking similarities to the in vivo microdissected tibiae screen; however, the micromass system was unable to accurately distinguish gene expression differences in the hypertrophic and mineralized zones of the growth plate. These studies will allow us to better understand zone-specific gene expression patterns in the growth plate. Ultimately, this work will help define both the genomic context in which genes are expressed in the long bones and the extent to which the micromass culture system is able to recapitulate chondrocyte development in endochondral ossification. Experiment Overall Design: Tibiae from 15.5 day old mouse embryos were isolated and partitioned into three distinct zones. Total RNA was isolated from each segment and the individual segments pooled within a litter. Experiment Overall Design: Samples were hybridized to Affymetrix MOE 430 2.0 mouse chips for analysis. Four independent trials were executed for each zone. Experiment Overall Design: Number of time points: 1 Experiment Overall Design: Number of treatments: 0 Experiment Overall Design: Number of Samples: 4 replicates per zone Experiment Overall Design: Affymetrix chip: MOE 430 2.0 Experiment Overall Design: Tissue or origin: Tibiae Experiment Overall Design: Species E15.5 mice Experiment Overall Design: Samples: Total RNA

Dataset Information

The Local CNP/GC-B system in growth plate is responsible for physiological endochondral bone growth.

Publications

The Local CNP/GC-B system in growth plate is responsible for physiological endochondral bone growth.

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