Search

Normal bone remodeling is a continuous process orchestrated by bone-resorbing osteoclasts and bone-forming osteoblasts, which an imbalance in bone remodeling results in metabolic bone diseases. RANKL, a member of the TNF cytokine family, functions as a key stimulator for osteoclast differentiation and maturation. Here, we report that RNF114, previously identified as a psoriasis susceptibility gene, plays a regulatory role in the RANKL/RANK/TRAF6 signaling pathway that mediates osteoclastogenesis. Our results demonstrated that RNF114 expression was significantly down-regulated in mouse osteoclast precursor cells undergoing RANKL-induced osteoclast differentiation. RNF114 knockout did not affect development or viability of the subpopulation of bone marrow macrophages capable of differentiating into osteoclasts in culture. However, in the presence of RANKL, RNF114 knockout bone marrow macrophages exhibited enhanced cell proliferation and augmented osteoclast differentiation, as shown by an increased expression of mature osteoclast markers, increased osteoclastic TRAP activity and bone resorption. Conversely, ectopic expression of RNF114 inhibited CTSK expression, TRAP activity, and bone resorption in RANKL-treated pre-osteoclasts. RNF114 also suppressed RANKL-activated NFATc1 expression and NFAT-regulated promoter activity. RNF114 suppressed TRAF6-, but not TAK1/TAB2-mediated NF-κB activation downstream of RANKL/RANK. In particular, TRAF6 protein levels were down-regulated by RNF114, possibly via K48-mediated proteasome-dependent degradation. These data suggested that RNF114's inhibitory effect on RANKL-stimulated osteoclastogenesis was mediated by blocking RANK/TRAF6/NF-κB signal transduction. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:159-166, 2018.

Internal disc disruption and annular tears are some of the causes of back and leg pain. It is difficult to observe location of internal damage and its distribution and propagation in cadaveric experiments or via imaging in clinical scenarios. Finite element analysis is useful for understanding the effects of different loading conditions on the location of initiation and propagation of tears in the annulus. In this study, a hyperelastic anisotropic material model in conjunction with biaxial properties was used for modelling annulus fibrosus material under a variety of loading conditions. The loading conditions considered included compression, flexion, extension, and their combinations. Tsai-Wu criterion was used to evaluate the damage, considering strength anisotropy and asymmetry. Damage predictions based on this criterion are in better agreement with available experimental studies and clinical observations, as compared to other approaches. Therefore, the use of Tsai-Wu criterion is suggested as an appropriate mechanical parameter to quantify damage, its initiation locations, and its distribution in annulus fibrosus under different loading conditions. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:113-122, 2017.