Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell
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RESEARCH ARTICLE
Open Access
Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro Roman M. Natoli1,2, Henry Yu1, Megan Conti-Mica Meislin1,3, Pegah Abbasnia1,4, Philip Roper1, Aleksandra Vuchkovska1, Xianghui Xiao5, Stuart R. Stock6 and John J. Callaci1*
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, rOPNmediated 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. Keywords: Bone fracture, Fracture non-union, Alcohol, Osteopontin, Integrin, Mesenchymal stem cell migration
Background While most patients suffering a bone fracture enjoy an uncomplicated recovery, impaired fracture healing [delayed union, non-union] occurs in approximately 5–10% of patients [1], with up to 19% of patients with open tibial shaft fractures progressing to non-union. [2]. There are several factors that contribute to impaired fracture healing, one of which is excessive alcohol consumption [3–6]. Patients with non-unions have increased morbidity [7] * Correspondence: [email protected] 1 Department of Orthopaedic Surgery and Rehabilitation, Stritch School of Medicine, Loyola University Chicago, 2160 South First Ave, Maywood, IL 60153, USA Full list of author information is available at the end of the article
and often require further surgical interventions, which have limited efficacy and are costly to the healthcare system. Understanding the biology of alcohol-impaired fracture healing may lead to the development of non-surgical strategies to prevent or reverse the process. Alcohol consu
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