Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro

Roman M. Natoli, Henry Yu, Megan Conti Mica Meislin, Pegah Abbasnia, Philip Roper, Aleksandra Vuchkovska, Xianghui Xiao, Stuart R Stock, John J. Callaci

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Alcohol consumption is a risk factor for impaired fracture healing, though the mechanism(s) by which this occurs are not well understood. Our laboratory has previously shown that episodic alcohol exposure of rodents negatively affects fracture callus development, callus biomechanics, and cellular signaling which regulates stem cell differentiation. Here, we examine whether alcohol alters chemokine expression and/or signaling activity in the mouse fracture callus during early fracture healing. Methods: A mouse model for alcohol-impaired tibia fracture healing was utilized. Early fracture callus was examined for alcohol-effects on tissue composition, expression of chemokines involved in MSC migration to the fracture site, and biomechanics. The effects of alcohol on MSC migration and cell adhesion receptors were examined in an in vitro system. Results: Mice exposed to alcohol showed decreased evidence of external callus formation, decreased callus-related osteopontin (OPN) expression levels, and decreased biomechanical stiffness. Alcohol exposure decreased rOPN-mediated MSC migration and integrin β1 receptor expression in vitro. Conclusions: The effects of alcohol exposure demonstrated here on fracture callus-associated OPN expression, rOPN-mediated MSC migration in vitro, and MSC integrin β1 receptor expression in vitro have not been previously reported. Understanding the effects of alcohol exposure on the early stages of fracture repair may allow timely initiation of treatment to mitigate the long-term complications of delayed healing and/or fracture non-union.

Original languageEnglish (US)
Article number101
JournalJournal of Orthopaedic Surgery and Research
Volume13
Issue number1
DOIs
StatePublished - Apr 27 2018

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Osteopontin
Fracture Healing
Mesenchymal Stromal Cells
Cell Movement
Bony Callus
Alcohols
Chemokines
Biomechanical Phenomena
Integrins
In Vitro Techniques
Tibia
Cell Adhesion
Alcohol Drinking
Cell Differentiation
Rodentia
Stem Cells

Keywords

  • Alcohol
  • Bone fracture
  • Fracture non-union
  • Integrin
  • Mesenchymal stem cell migration
  • Osteopontin

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

Natoli, Roman M. ; Yu, Henry ; Meislin, Megan Conti Mica ; Abbasnia, Pegah ; Roper, Philip ; Vuchkovska, Aleksandra ; Xiao, Xianghui ; Stock, Stuart R ; Callaci, John J. / Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro. In: Journal of Orthopaedic Surgery and Research. 2018 ; Vol. 13, No. 1.
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Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro. / Natoli, Roman M.; Yu, Henry; Meislin, Megan Conti Mica; Abbasnia, Pegah; Roper, Philip; Vuchkovska, Aleksandra; Xiao, Xianghui; Stock, Stuart R; Callaci, John J.

In: Journal of Orthopaedic Surgery and Research, Vol. 13, No. 1, 101, 27.04.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro

AU - Natoli, Roman M.

AU - Yu, Henry

AU - Meislin, Megan Conti Mica

AU - Abbasnia, Pegah

AU - Roper, Philip

AU - Vuchkovska, Aleksandra

AU - Xiao, Xianghui

AU - Stock, Stuart R

AU - Callaci, John J.

PY - 2018/4/27

Y1 - 2018/4/27

N2 - Background: Alcohol consumption is a risk factor for impaired fracture healing, though the mechanism(s) by which this occurs are not well understood. Our laboratory has previously shown that episodic alcohol exposure of rodents negatively affects fracture callus development, callus biomechanics, and cellular signaling which regulates stem cell differentiation. Here, we examine whether alcohol alters chemokine expression and/or signaling activity in the mouse fracture callus during early fracture healing. Methods: A mouse model for alcohol-impaired tibia fracture healing was utilized. Early fracture callus was examined for alcohol-effects on tissue composition, expression of chemokines involved in MSC migration to the fracture site, and biomechanics. The effects of alcohol on MSC migration and cell adhesion receptors were examined in an in vitro system. Results: Mice exposed to alcohol showed decreased evidence of external callus formation, decreased callus-related osteopontin (OPN) expression levels, and decreased biomechanical stiffness. Alcohol exposure decreased rOPN-mediated MSC migration and integrin β1 receptor expression in vitro. Conclusions: The effects of alcohol exposure demonstrated here on fracture callus-associated OPN expression, rOPN-mediated MSC migration in vitro, and MSC integrin β1 receptor expression in vitro have not been previously reported. Understanding the effects of alcohol exposure on the early stages of fracture repair may allow timely initiation of treatment to mitigate the long-term complications of delayed healing and/or fracture non-union.

AB - Background: Alcohol consumption is a risk factor for impaired fracture healing, though the mechanism(s) by which this occurs are not well understood. Our laboratory has previously shown that episodic alcohol exposure of rodents negatively affects fracture callus development, callus biomechanics, and cellular signaling which regulates stem cell differentiation. Here, we examine whether alcohol alters chemokine expression and/or signaling activity in the mouse fracture callus during early fracture healing. Methods: A mouse model for alcohol-impaired tibia fracture healing was utilized. Early fracture callus was examined for alcohol-effects on tissue composition, expression of chemokines involved in MSC migration to the fracture site, and biomechanics. The effects of alcohol on MSC migration and cell adhesion receptors were examined in an in vitro system. Results: Mice exposed to alcohol showed decreased evidence of external callus formation, decreased callus-related osteopontin (OPN) expression levels, and decreased biomechanical stiffness. Alcohol exposure decreased rOPN-mediated MSC migration and integrin β1 receptor expression in vitro. Conclusions: The effects of alcohol exposure demonstrated here on fracture callus-associated OPN expression, rOPN-mediated MSC migration in vitro, and MSC integrin β1 receptor expression in vitro have not been previously reported. Understanding the effects of alcohol exposure on the early stages of fracture repair may allow timely initiation of treatment to mitigate the long-term complications of delayed healing and/or fracture non-union.

KW - Alcohol

KW - Bone fracture

KW - Fracture non-union

KW - Integrin

KW - Mesenchymal stem cell migration

KW - Osteopontin

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