title: CCR2 elimination in mice results in larger and stronger tibial bones but bone loss is not attenuated following ovariectomy or muscle denervation.
abstract: Bone loss due to age and disuse contributes to osteoporosis and increases fracture risk. It has been hypothesized that such bone loss can be attenuated by modulation of the C-C chemokine receptor 2 (CCR2) and/or its ligands. The objectives of this study were to examine the effects of genetic elimination of CCR2 on cortical and trabecular bones in the mouse tibia and how bone loss was impacted following disuse and estrogen loss. Female CCR2 knockout (CCR2(-/-)) and wildtype mice underwent ovariectomy (OVX) or denervation of musculature adjacent to the tibia (DEN) to induce bone loss. Cortical and trabecular structural properties as well as mechanical properties (i.e., strength) of tibial bones were measured. Compared to wildtype mice, CCR2(-/-) mice had tibiae that were up to 9% larger and stronger; these differences could be explained mainly by the 17% greater body mass (P < 0.001) of CCR2(-/-) mice. The majority of the tibia's structural and functional responses to OVX and DEN were similar regardless of the lack or presence of CCR2, indicating that CCR2 is not protective against bone loss per se. These findings indicate that while CCR2(-/-) mice do have larger and stronger bones than do wildtype mice, there is minimal evidence that CCR2 elimination provides protection against bone loss during disuse and estrogen loss.
authors.affiliation: Rehabilitation Science and Program in Physical Therapy, University of Minnesota, Minneapolis, MN, USA, mede0016@umn.edu.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Mader
authors.forename: Susan A
authors.initials: SA
authors.lastname: Novotny
authors.forename: Angela S
authors.initials: AS
authors.lastname: Lin
authors.forename: Robert E
authors.initials: RE
authors.lastname: Guldberg
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Lowe
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Warren
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009121:Muscle Denervation; D010024:Osteoporosis / Q000235:genetics / Q000378:metabolism*; D010052:Ovariectomy; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D013977:Tibia / Q000033:anatomy & histology* / Q000378:metabolism*; D055114:X-Ray Microtomography
chemical_list: C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2