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MacKay, Danielle L.; Kean, Thomas J.; Bernardi, Kristina G.; Haeberle, Heather S.; Ambrose, Catherine G.; Lin, Feng; Dennis, James E.

Reduced bone loss in a murine model of postmenopausal osteoporosis lacking complement component 3

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  • Medientyp: E-Artikel
  • Titel: Reduced bone loss in a murine model of postmenopausal osteoporosis lacking complement component 3
  • Beteiligte: MacKay, Danielle L.; Kean, Thomas J.; Bernardi, Kristina G.; Haeberle, Heather S.; Ambrose, Catherine G.; Lin, Feng; Dennis, James E.
  • Erschienen: Wiley, 2018
  • Erschienen in: Journal of Orthopaedic Research
  • Sprache: Englisch
  • DOI: 10.1002/jor.23643
  • ISSN: 1554-527X; 0736-0266
  • Schlagwörter: Orthopedics and Sports Medicine
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>ABSTRACT</jats:title><jats:sec><jats:label /><jats:p>The growing field of osteoimmunology seeks to unravel the complex interdependence of the skeletal and immune systems. Notably, we and others have demonstrated that complement signaling influences the differentiation of osteoblasts and osteoclasts, the two primary cell types responsible for maintaining bone homeostasis. However, the net effect of complement on bone homeostasis in vivo was unknown. Our published in vitro mechanistic work led us to hypothesize that absence of complement component 3 (C3), a central protein in the complement activation cascade, protects against bone loss in the ovariectomy‐based model of postmenopausal osteoporosis. Indeed, we report here that, when compared to their C57BL/6J (WT) counterparts, ovariectomized C3 deficient mice experienced reduced bone loss at multiple sites and increased stiffness at the femoral neck, the latter potentially improving mechanical function. WT and B6;129S4‐C3<jats:sup><jats:italic>tm</jats:italic></jats:sup><jats:italic><jats:sup>1</jats:sup></jats:italic><jats:sup><jats:italic>Crr</jats:italic></jats:sup>/J (C3<jats:sup>‐/‐</jats:sup>) mice were either ovariectomized or sham‐operated at 6 weeks of age and euthanized at 12 weeks. MicroCT on harvested bones revealed that the trabecular bone volume fraction in the metaphyses of both the proximal tibiae and distal femora of ovariectomized C3<jats:sup>‐/‐</jats:sup> mice is significantly greater than that of their WT counterparts. Lumbar vertebrae showed significantly greater osteoid content and mineral apposition rates. Mechanical testing demonstrated significantly greater stiffness in the femoral necks of ovariectomized C3<jats:sup>‐/‐</jats:sup> mice. These results demonstrate that C3 deficiency reduces bone loss at ovariectomy and may improve mechanical properties. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:118–128, 2018.</jats:p></jats:sec>