Mouse fibroblast growth factor 9 N143T mutation leads to wide chondrogenic condensation of long bones

Long bones of the appendicular skeleton are formed through endochondral ossification. Endochondral bone formation initiates with mesenchymal condensation, followed by the formation of a cartilage template which is replaced by bone. Fibroblast growth factor 9 (FGF9) regulates bone development. Fgf9 −...

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Published inHistochemistry and cell biology Vol. 153; no. 4; pp. 215 - 223
Main Authors Harada, Masayo, Akita, Keiichi
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2020
Springer Nature B.V
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Summary:Long bones of the appendicular skeleton are formed through endochondral ossification. Endochondral bone formation initiates with mesenchymal condensation, followed by the formation of a cartilage template which is replaced by bone. Fibroblast growth factor 9 (FGF9) regulates bone development. Fgf9 −/− mice exhibit disproportionate shortening of proximal skeletal elements. Fgf9 missense mutations in mice and humans induce joint synostosis. Thus, FGF9 is critical for regulating bone length and joint formation. Conversely, mechanisms regulating bone width remain unclear. Here, we showed that the homozygous elbow knee synostosis (Eks) mutant mice harboring N143T mutation in Fgf9 have wide long bones at birth. We investigated the cellular and molecular mechanisms underlying the widened prospective humerus in Fgf9 Eks/Eks embryos. Increased and expanded FGF signaling in concert with wider expression domain of Fgf receptor 3 ( Fgfr3 ) during chondrogenic condensation of the humerus led to widened cartilage, which resulted in the formation of wider prospective humeri in neonatal Fgf9 Eks/Eks mice. Increased and expanded FGF signaling during chondrogenic condensation led to increased density of chondrocytes of the humeri accompanied by increased proliferation of chondrocytes which express inappropriately higher levels of cyclin D1 in Fgf9 Eks/Eks embryos. The results suggest that FGF9 regulates the width of prospective long bones by controlling the width of chondrogenic condensation.
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ISSN:0948-6143
1432-119X
DOI:10.1007/s00418-020-01844-2