TNFalpha and IL-1alpha are potent stimulators of bone resorption in vivo and in vitro. Recently, it has been demonstrated that these two cytokines directly induce osteoclastogenesis in mouse marrow cultures. This study determined whether TNFalpha (+/- IL-1alpha) is also capable of inducing human osteoclastogenesis. The CD14(+) monocyte fraction of human peripheral mononuclear cells was cultured with TNFalpha +/- IL-1alpha in the presence of M-CSF. TNFalpha induced the formation of multinucleated cells (MNCs) which were positive for TRAP, VNR and cathepsin K and showed evidence of resorption pit formation. IL-1alpha stimulated TNFalpha-induced lacunar resorption two- to four-fold. Osteoprotegerin, the decoy receptor for RANKL, did not inhibit this process. Anti-human IL-1alpha neutralizing antibodies significantly inhibited resorption without inhibiting the formation of TRAP(+)/VNR(+) MNCs. These results suggest that, in the presence of M-CSF, TNFalpha is sufficient for inducing human osteoclast differentiation from circulating precursors by a process which is distinct from the RANK/RANKL signalling pathway.
Aseptic loosening and failure of a tibial component are recognized problems in unicompartmental knee arthroplasty (UKA). Excessive stress on the supporting cancellous bone is thought to contribute to the loosening and failure. Of factors that could influence supporting cancellous bone stresses, we focused on the inclination of a unicompartmental tibial component by analyzing the effect of coronal plane and sagittal plane inclination. Detailed geometrically accurate, three-dimensional finite element models were constructed from computed tomography (CT) data of a typical adult male proximal tibia. The material properties for the models were obtained directly from the CT data to simulate the inhomogeneous distribution of cancellous bone properties. Placing the component in slight valgus inclination in the coronal plane reduced the cancellous bone stresses. Posterior inclination in the sagittal plane caused a moderate increase in the stresses. Our results suggest that slight valgus inclination of a UKA tibial component may be preferable to varus or square inclination in the coronal plane. An excessive posterior slope of a tibial component should be avoided.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.