Incorporation of Cerium Oxide into Hydroxyapatite Coating Protects Bone Marrow Stromal Cells Against H 2 O 2 -Induced Inhibition of Osteogenic Differentiation.

Oxidative stress exerts a key influence in osteoporosis in part by inhibiting osteogenic differentiation of bone marrow stromal cells (BMSCs). With their unique antioxidant properties and reported biocompatibility, cerium oxide (CeO2 ) ceramics exhibit promising potential for the treatment of osteoporosis resulting from oxidative stress. In this study, protective effects of CeO2 -incorporated hydroxyapatite coatings (HA-10Ce and HA-30Ce) on the viability and osteogenic differentiation of H2 O2 -treated BMSCs were examined. CeO2 -incorporated HA coatings enhanced cell viability and attenuated cell apoptosis caused by H2 O2 . An increase in CeO2 content in HA coatings better alleviated H2 O2 -induced inhibition of osteogenic differentiation by increasing alkaline phosphatase (ALP) activity, calcium deposition activity, and mRNA expression levels of osteogenesis markers runt-related transcription factor 2 (Runx2), ALP, and osteocalcin (OCN) in BMSCs. Furthermore, the H2 O2 -induced decrease of gene and protein expressions of β-catenin and cyclin D1 in the Wnt/β-catenin signaling pathway was successfully rescued by the CeO2 incorporated HA coatings. Besides, the decreased expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and the increased ratio of osteoprotegerin (OPG)/RANKL in BMSCs on the CeO2 -modified coatings was observed, indicating the inhibition of osteoclastogenesis. The above results were mediated by the antioxidant properties of CeO2 . The CeO2 -incorporated HA coatings reversed the decreased superoxide dismutase (SOD) activity, reduced reactive oxygen species (ROS) generation, and suppressed the malondiadehyde (MDA) formation. The findings suggested that CeO2 -modified HA coatings may be promising coating materials for osteoporotic bone regeneration.