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 in | Histochemistry and cell biology Vol. 153; no. 4; pp. 215 - 223 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.04.2020
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0948-6143 1432-119X |
DOI: | 10.1007/s00418-020-01844-2 |