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

Alberto Rosello-Diez, Daniel Stephen, Alexandra L. Joyner

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article numbere27210
Number of pages24
JournaleLife
Volume6
DOIs
Publication statusPublished - 25 Jul 2017
Externally publishedYes

Cite this

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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.",
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Altered paracrine signaling from the injured knee joint impairs postnatal long bone growth. / Rosello-Diez, Alberto; Stephen, Daniel; Joyner, Alexandra L.

In: eLife, Vol. 6, e27210, 25.07.2017.

Research output: Contribution to journalArticleResearchpeer-review

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