The Proprioceptive System Regulates Morphologic Restoration of Fractured Bones

Ronen Blecher, Sharon Krief, Tal Galili, Eran Assaraf, Tomer Stern, Yoram Anekstein, Gabriel Agar, Elazar Zelzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Successful fracture repair requires restoration of bone morphology and mechanical integrity. Recent evidence shows that fractured bones of neonatal mice undergo spontaneous realignment, dubbed “natural reduction.” Here, we show that natural reduction is regulated by the proprioceptive system and improves with age. Comparison among mice of different ages revealed, surprisingly, that 3-month-old mice exhibited more rapid and effective natural reduction than newborns. Fractured bones of null mutants for transcription factor Runx3, lacking functional proprioceptors, failed to realign properly. Blocking Runx3 expression in the peripheral nervous system, but not in limb mesenchyme, recapitulated the null phenotype, as did inactivation of muscles flanking the fracture site. Egr3 knockout mice, which lack muscle spindles but not Golgi tendon organs, displayed a less severe phenotype, suggesting that both receptor types, as well as muscle contraction, are required for this regulatory mechanism. These findings uncover a physiological role for proprioception in non-autonomous regulation of skeletal integrity.

Original languageEnglish
Pages (from-to)1775-1783
Number of pages9
JournalCell Reports
Volume20
Issue number8
DOIs
StatePublished - 22 Aug 2017

Funding

FundersFunder number
E.Z.
Israel Cancer Research Fund
Bernard van Leer Foundation
Audrey and Theodor Geisel School of Medicine at Dartmouth
Life Sciences Research Foundation
Spine Foundation
Seventh Framework Programme310098
European Research Council
Weizmann Institute of Science
Dan David Prize
Nella and Leon Benoziyo Center for Neurological Diseases, Weizmann Institute of Science

    Keywords

    • Egr3
    • Golgi tendon organs
    • Runx3
    • dorsal root ganglia
    • fracture repair
    • mouse
    • muscle spindles
    • proprioception

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