Incorporation of cerium oxide into zirconia toughened alumina ceramic promotes osteogenic differentiation and osseointegration.

Due to its high wear resistance and good biocompatibility, zirconia toughened alumina (ZTA) is an ideal material used as load-bearing implant. However, ZTA needs to be modified to overcome its bio-inert and thus improve osseointegration. Cerium oxide, which has been proved to be a bone-friendly ceramic, might be a desired material to enhance the bioactivity of ZTA. In this study, ZTA and cerium oxide doped ZTA (ZTAC) were prepared via sintering method. The in vitro study showed that the addition of cerium oxide promoted MC3T3-E1 cell adhesion and spreading through upregulating ITG α5 and ITG ß1. In addition, the incorporation of cerium oxide enhanced cell proliferation, ALP activity, and ECM mineralization capacity. Moreover, the incorporation of cerium oxide promoted the expressions of osteogenesis related genes, such as ALP, Col-I, and OCN. The in vivo implantation test via a SD rat model showed that the incorporation of cerium oxide promoted new bone formation and bone-implant integration. In summary, this study provided a new strategy to fabricate bioactive ZTA implant for potential application in orthopedics field.

Vindoline Attenuates Osteoarthritis Progression Through Suppressing the NF-κB and ERK Pathways in Both Chondrocytes and Subchondral Osteoclasts.

Disruption of extracellular matrix (ECM) homeostasis and subchondral bone remodeling play significant roles in osteoarthritis (OA) pathogenesis. Vindoline (Vin), an indole alkaloid extracted from the medicinal plant Catharanthus roseus, possesses anti-inflammatory properties. According to previous studies, inflammation is closely associated with osteoclast differentiation and the disorders of the homeostasis between ECM. Although Vin has demonstrated effective anti-inflammatory properties, its effects on the progression of OA remain unclear. We hypothesized that Vin may suppress the progress of OA by suppressing osteoclastogenesis and stabilizing ECM of articular cartilage. Therefore, we investigated the effects and molecular mechanisms of Vin as a treatment for OA in vitro and in vivo. In the present study, we found that Vin significantly suppressed RANKL-induced osteoclast formation and obviously stabilized the disorders of the ECM homeostasis stimulated by IL-1ß in a dose-dependent manner. The mRNA expressions of osteoclast-specific genes were inhibited by Vin treatment. Vin also suppressed IL-1ß-induced mRNA expressions of catabolism and protected the mRNA expressions of anabolism. Moreover, Vin notably inhibited the activation of RANKL-induced and IL-1ß-induced NF-κB and ERK pathways. In vivo, Vin played a protective role by inhibiting osteoclast formation and stabilizing cartilage ECM in destabilization of the medial meniscus (DMM)-induced OA mice. Collectively, our observations provide a molecular-level basis for Vin's potential in the treatment of OA.

Toosendanin induces the apoptosis of human Ewing's sarcoma cells via the mitochondrial apoptotic pathway.

Toosendanin, a triterpenoid extracted from the root bark of Melia toosendan, has its origin from traditional Chinese medicine and has been used as a non­polluting and pesticide­free plant insecticide in China for fruit and vegetable production. In recent years, toosendanin has been found to inhibit tumor cell proliferation and promote tumor cell apoptosis. Ewing's sarcoma (ES) is the second most common primary malignant bone and soft tissue tumor in children and adolescents. Although the overall prognosis of ES has improved, the 5­year survival rate has not significantly increased. To analyze the role of toosendanin on ES progression, CCK­8 viability assay, flow cytometry, Hoechst 33258 staining and western blotting were performed. The present results suggested that toosendanin suppressed cell viability and induced apoptosis in human SK­ES­1 cells compared with DMSO treatment. In addition, in the present study, toosendanin was found to upregulate the expression of Bax and downregulate the expression of Bcl­2, altering the Bax/Bcl­2 ratio. Additionally, toosendanin promoted the release of cytochrome c, resulting in the activation of the mitochondrial apoptotic pathway, thus inducing the activation of caspase­9 and caspase­3, and the cleavage of PARP. Our results demonstrated that toosendanin inhibited the growth of ES cells in a dose­dependent manner and triggered mitochondrial apoptotic pathway to induce apoptosis. Therefore, toosendanin can potentially be utilized as an anticancer botanical drug for the treatment of ES.