title: Focal enhancement of the skeleton to exercise correlates with responsivity of bone marrow mesenchymal stem cells rather than peak external forces.
abstract: Force magnitudes have been suggested to drive the structural response of bone to exercise. As importantly, the degree to which any given bone can adapt to functional challenges may be enabled, or constrained, by regional variation in the capacity of marrow progenitors to differentiate into bone-forming cells. Here, we investigate the relationship between bone adaptation and mesenchymal stem cell (MSC) responsivity in growing mice subject to exercise. First, using a force plate, we show that peak external forces generated by forelimbs during quadrupedal locomotion are significantly higher than hindlimb forces. Second, by subjecting mice to treadmill running and then measuring bone structure with μCT, we show that skeletal effects of exercise are site-specific but not defined by load magnitudes. Specifically, in the forelimb, where external forces generated by running were highest, exercise failed to augment diaphyseal structure in either the humerus or radius, nor did it affect humeral trabecular structure. In contrast, in the ulna, femur and tibia, exercise led to significant enhancements of diaphyseal bone areas and moments of area. Trabecular structure was also enhanced by running in the femur and tibia. Finally, using flow cytometry, we show that marrow-derived MSCs in the femur are more responsive to exercise-induced loads than humeral cells, such that running significantly lowered MSC populations only in the femur. Together, these data suggest that the ability of the progenitor population to differentiate toward osteoblastogenesis may correlate better with bone structural adaptation than peak external forces caused by exercise.
authors.affiliation: Department of Anthropology, Stony Brook University, Stony Brook, NY 11794, USA iwallace@fas.harvard.edu.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Wallace
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Pagnotti
authors.affiliation: Department of Anatomical Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Jasper
authors.initials: J
authors.lastname: Rubin-Sigler
authors.affiliation: Department of Anthropology, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Naeher
authors.affiliation: Department of Medical Sciences, Quinnipiac University, Hamden, CT 06518, USA.
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Copes
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Judex
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Clinton T
authors.initials: CT
authors.lastname: Rubin
authors.affiliation: Department of Anatomical Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Demes
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000033:anatomy & histology / Q000502:physiology*; D005260:Female; D005552:Forelimb; D006614:Hindlimb; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009043:Motor Activity / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010805:Physical Conditioning, Animal
keywords: Bone adaptation; Cortical bone; Ground reaction forces; Mechanical loading; Osteoprogenitor cells; Physical activity; Trabecular bone