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Altered paracrine signaling from the injured knee joint impairs postnatal long bone growth.

Published version
Peer-reviewed

Repository DOI


Type

Article

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Authors

Roselló-Díez, Alberto  ORCID logo  https://orcid.org/0000-0002-5550-9846
Stephen, Daniel 
Joyner, Alexandra L  ORCID logo  https://orcid.org/0000-0001-7090-9605

Abstract

Regulation of organ growth is a poorly understood process. In the long bones, the growth plates (GPs) drive elongation by generating a scaffold progressively replaced by bone. Although studies have focused on intrinsic GP regulation, classic and recent experiments suggest that local signals also modulate GP function. We devised a genetic mouse model to study extrinsic long bone growth modulation, in which injury is specifically induced in the left hindlimb, such that the right hindlimb serves as an internal control. Remarkably, when only mesenchyme cells surrounding postnatal GPs were killed, left bone growth was nevertheless reduced. GP signaling was impaired by altered paracrine signals from the knee joint, including activation of the injury response and, in neonates, dampened IGF1 production. Importantly, only the combined prevention of both responses rescued neonatal growth. Thus, we identified signals from the knee joint that modulate bone growth and could underlie establishment of body proportions.

Description

Keywords

connective tissue, developmental biology, extrinsic signaling, growth plate, inflammation, injury response, mouse, organ size, stem cells, Animals, Bone Development, Disease Models, Animal, Insulin-Like Growth Factor I, Knee Injuries, Mice, Paracrine Communication

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

6

Publisher

eLife Sciences Publications, Ltd