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 found-unaltered 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.