RESUMO
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.
Assuntos
Óxido de Alumínio , Cério , Animais , Cerâmica , Osseointegração , Osteogênese/fisiologia , Ratos , Ratos Sprague-Dawley , ZircônioRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Glaucocalyxin A (GLA), the most abundant active component of the aboveground sections of Rabdosia japonica (Burm. f.) Hara var. glaucocalyx (Maxim.) Hara, possesses various pharmacological activities, such as antioxidant, antithrombosis, anticoagulation, antibacterial, antitumor, anti-inflammatory activities. According to previous studies, inflammation is closely associated with osteoclast differentiation and activity. Although GLA has demonstrated effective anti-inflammatory properties, its effects on osteoclast differentiation remain unclear. AIM OF THE STUDY: To examine the possible inhibitory effects of GLA and its molecular mechanisms in osteogenesis induced by RANKL as well as ovariectomy (OVX)-induced osteoporosis (OP) in mice. MATERIALS AND METHODS: Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining, and a bone resorption pit assay were applied for identifying the effects of GLA on the differentiation of osteoclasts and the function of bone resorption. The mRNA expression of the genes related to osteoclast differentiation was measured by quantitative PCR. Protein expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), c-fos and phosphorylation of inhibitor of nuclear factor kappa B (IκBα), protein kinase B (AKT), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 in RANKL-induced osteoclasts was determined using western blotting. The effect of GLA on OP was studied using a mouse model of OVX. RESULTS: At nontoxic concentrations ≤0.5 µM in vitro, GLA suppressed the formation of osteoclasts induced by RANKL with the decreased number and area size of TRAP-positive multinuclear osteoclasts, and the resorption of bone function by reducing F-actin ring number and bone resorption pit areas. It also reduced the expression of the genes specific for osteoclasts, which included genes encoding NFATc1, cathepsin K, c-fos, TRAP, vacuolar-type ATPase d2, and dendritic cell-specific transmembrane protein. Moreover, GLA repressed NF-κB and Akt pathway activation induced by RANKL. Micro-CT analysis of femur samples indicated decreased bone loss and greater trabecular bone density after GLA treatment, which showed that GLA played a protective role by inhibiting bone loss in OVX-induced OP mice in vivo. CONCLUSIONS: Our study is the first to show that GLA has significant therapeutic potential in OP, which is the disease of osteoclast increase caused by estrogen deficiency.