Genetic elimination of CCR2 provides minimal protection of bone functional capacity

Abstract

Chemokines are proposed to be involved with bone loss. The purpose of this study was to determine whether genetic elimination of C-C chemokine receptor 2 (CCR2) was protective of bone geometry and function. Ovariectomy and denervation were used as interventions to induce bone loss in mice with and without CCR2 (C57BL/6 wild type and CCR2-knockout (CCR2-/-) mice, respectively). Cortical geometry and trabecular morphology of tibial bones were determined using μCT analyses. Bone mechanical properties were calculated from load displacement curves using 3-point bending testing. Overall, the elimination of CCR2 had a minor protective effect on bone mechanical properties. CCR2-/- mice had bones slightly larger and stronger than C57BL/6 mice. In ovariectomized and denervated mice, CCR2-/- tibiae exhibited 5-18% greater cross sectional area, cross sectional moment of inertia, ultimate load, and stiffness than C57BL/6 tibiae indicating a resistance to intervention-induced bone loss in the CCR2-/- mice. Trabecular bone volume fraction and bone mineral density was 2-22% greater in CCR2-/- mice than C57BL/6 mice at both the epiphysis and the metaphysis. Additionally, periosteal diameter was protected in CCR2-/- mice but not in C57BL/6 mice with interventions. It is concluded that genetic elimination of CCR2 results in larger bones that are minimally protected under conditions of induced bone loss.