Effect of Host Sex and Sex Hormones on Muscle-Derived Stem Cell-Mediated Bone Formation and Defect Healing

Abstract

Muscle-derived stem cells (MDSCs) are known to exhibit sexual dimorphism, by donor sex, of osteogenic, chondrogenic, and myogenic differentiation potential in vitro. Moreover, host sex differences in the myogenic capacity of MDSCs in vivo are also observed. This study investigated the role of host sex and host sex hormones in MDSC-mediated bone formation and healing. Using unaltered male, castrated male, unaltered female, and ovariectomized female mice, both MDSC-mediated ectopic bone formation and cranial defect healing were examined. Male hosts, whether unaltered or castrated, form significantly larger volumes of MDSC-mediated ectopic bone than female hosts (either unaltered or ovariectomized), and no differences in ectopic bone volume were found between hosts of the same sex. In a cranial defect healing model, similar results were foundunaltered and castrated male hosts display larger volumes of bone formed when compared with unaltered and ovariectomized female hosts. However, in this healing model, some volume differences were found between hosts of the same sex. In both models, these differences were attributed to varying rates of endochondral bone formation in male and female hosts.

Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7

“…The potential of mesenchymal progenitor cells to differentiate into osteoprogenitor cells in muscles, has been shown in animal models[20-22]. In a resent in vitro study human skeletal muscle-derived progenitor cells have been isolated and characterized for their osteogenic properties indicating a potential effect on heterotopic bone formatio[23].…”

Surgically-induced mouse models in the study of bone regeneration: Current models and future directions

“…A review of the literature revealed that two of the most frequently used methods to establish a critical bone defect include the use of either the cranial bone of the skull (38,39) or long bones of the extremities, including the femur (25,40,41) and radius. There are various differences in the methods used to establish these models.…”

Comparação entre fontes de células-tronco mesenquimais na indução à regeneração óssea

“…A dificuldade em separar o biomaterial do osso neoformado foi observada por YE e colaboradores (2012) ;MESZAROS et al, 2012;SHEN et al, 2004;WRIGHT et al, 2002).…”

“…Sendo assim, a menor neoformação óssea observada nos lados em que foram enxertadas OOMDSC não podem ser explicadas pela ausência destas células, visto que estas células ainda estão presentes no local do enxerto após 50 dias de cirurgia. Este resultado está em contradição com a maioria dos artigos da literatura, os quais tem mostrado que as células-tronco enxertadas, participam da regeneração óssea de defeitos críticos calvarianos (LAINO et al, 2006;MA et al, 2012;MESZAROS et al, 2012;PENG et al, 2002;SEO et al, 2008;WRIGHT et al, 2002;ZHENG et al, 2009 …”

“…Esta população inclui além da fibras musculares, células-tronco derivadas de músculo (MDSC). As MDSC são células multipotentes, capazes de se diferenciar em diversos tipos celulares, tais como os adipócitos, osteoblastos e condrócitos (JACKSON et al, 2011;JANKOWSKI et al, 2002;MASTROGIACOMO et al, 2005;SUN et al,, 2005 Além disto, alguns estudos na literatura sugerem que as neoformações ósseas podem ter como origem as MDSC enxertadas (LEE et al, 2001;MASTROGIACOMO et al, 2005;MUSGRAVE et al, 2002;WRIGHT et al, 2002) ou ainda ser um mosaico contendo porções de ambas as origens (MESZAROS et al, 2012).…”