α 1 adrenergic receptor agonist, phenylephrine, actively contracts early rat rib fracture callus ex vivo

Stuart J. McDonald, Philip C. Dooley, Aaron C. McDonald, Elvan Djouma, Johannes A. Schuijers, Alex R. Ward, Brian L. Grills

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Early, soft fracture callus that links fracture ends together is smooth muscle-like in nature. We aimed to determine if early fracture callus could be induced to contract and relax ex vivo by similar pathways to smooth muscle, that is, contraction via α 1 adrenergic receptor (α 1AR) activation with phenylephrine (PE) and relaxation via β 2 adrenergic receptor (β 2AR) stimulation with terbutaline. A sensitive force transducer quantified 7 day rat rib fracture callus responses in modified Krebs-Henseliet (KH) solutions. Unfractured ribs along with 7, 14, and 21 day fracture calluses were analyzed for both α 1AR and β 2AR gene expression using qPCR, whilst 7 day fracture callus was examined via immunohistochemistry for both α 1AR and β 2AR- immunoreactivity. In 7 day callus, PE (10 -6 M) significantly induced an increase in force that was greater than passive force generated in calcium-free KH (n = 8, mean 51% increase, 95% CI: 26-76%). PE-induced contractions in calluses were attenuated by the α 1AR antagonist, prazosin (10 -6 M; n = 7, mean 5% increase, 95% CI: 2-11%). Terbutaline did not relax callus. Gene expression of α 1ARs was constant throughout fracture healing; however, β 2AR expression was down-regulated at 7 days compared to unfractured rib (p < 0.01). Furthermore, osteoprogenitor cells of early fibrous callus displayed considerable α 1AR-like immunoreactivity but not β 2AR-like immunoreactivity. Here, we demonstrate for the first time that early fracture callus can be pharmacologically induced to contract. We propose that increased concentrations of α 1AR agonists such as noradrenaline may tonically contract callus in vivo to promote osteogenesis.

Original languageEnglish
Pages (from-to)740-745
Number of pages6
JournalJournal of Orthopaedic Research
Volume29
Issue number5
DOIs
Publication statusPublished - 1 May 2011

Keywords

  • adrenergic receptors
  • contraction
  • fracture healing
  • smooth muscle

Cite this

McDonald, Stuart J. ; Dooley, Philip C. ; McDonald, Aaron C. ; Djouma, Elvan ; Schuijers, Johannes A. ; Ward, Alex R. ; Grills, Brian L. / α 1 adrenergic receptor agonist, phenylephrine, actively contracts early rat rib fracture callus ex vivo. In: Journal of Orthopaedic Research. 2011 ; Vol. 29, No. 5. pp. 740-745.
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abstract = "Early, soft fracture callus that links fracture ends together is smooth muscle-like in nature. We aimed to determine if early fracture callus could be induced to contract and relax ex vivo by similar pathways to smooth muscle, that is, contraction via α 1 adrenergic receptor (α 1AR) activation with phenylephrine (PE) and relaxation via β 2 adrenergic receptor (β 2AR) stimulation with terbutaline. A sensitive force transducer quantified 7 day rat rib fracture callus responses in modified Krebs-Henseliet (KH) solutions. Unfractured ribs along with 7, 14, and 21 day fracture calluses were analyzed for both α 1AR and β 2AR gene expression using qPCR, whilst 7 day fracture callus was examined via immunohistochemistry for both α 1AR and β 2AR- immunoreactivity. In 7 day callus, PE (10 -6 M) significantly induced an increase in force that was greater than passive force generated in calcium-free KH (n = 8, mean 51{\%} increase, 95{\%} CI: 26-76{\%}). PE-induced contractions in calluses were attenuated by the α 1AR antagonist, prazosin (10 -6 M; n = 7, mean 5{\%} increase, 95{\%} CI: 2-11{\%}). Terbutaline did not relax callus. Gene expression of α 1ARs was constant throughout fracture healing; however, β 2AR expression was down-regulated at 7 days compared to unfractured rib (p < 0.01). Furthermore, osteoprogenitor cells of early fibrous callus displayed considerable α 1AR-like immunoreactivity but not β 2AR-like immunoreactivity. Here, we demonstrate for the first time that early fracture callus can be pharmacologically induced to contract. We propose that increased concentrations of α 1AR agonists such as noradrenaline may tonically contract callus in vivo to promote osteogenesis.",
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α 1 adrenergic receptor agonist, phenylephrine, actively contracts early rat rib fracture callus ex vivo. / McDonald, Stuart J.; Dooley, Philip C.; McDonald, Aaron C.; Djouma, Elvan; Schuijers, Johannes A.; Ward, Alex R.; Grills, Brian L.

In: Journal of Orthopaedic Research, Vol. 29, No. 5, 01.05.2011, p. 740-745.

Research output: Contribution to journalArticleResearchpeer-review

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