In the process of bone tissue engineering, the osteoimmunomodulatory property of biomaterials is very important for osteogenic differentiation of stem cells, which determines the outcome of bone regeneration. Magnesium (Mg) is a biodegradable, biocompatible metal that has osteoconductive properties and has been regarded as a promising bone biomaterial. However, the high degradation rate of Mg leads to excessive inflammation, thereby restricting its application in bone tissue engineering. Importantly, different coatings or magnesium alloys have been utilized to lower the rate of degradation. In fact, a prior study proved that β-TCP coating of Mg scaffolds can modulate the osteoimmunomodulatory properties of Mg-based biomaterials and create a favorable immune microenvironment for osteogenesis. However, the osteoimmunomodulatory properties of Mg ions themselves have not been explored yet. In this study, the osteoimmunomodulatory properties of Mg ions with involvement of macrophages and bone marrow stem cells (BMSCs) were systematically investigated. Microscale Mg ions (100 mg/L) were found to possess osteoimmunomodulatory properties that favor bone formation. Specifically, microscale Mg ions induced M2 phenotype changes of macrophages and the release of anti-inflammatory cytokines by inhibiting the TLR-NF-κB signaling pathway. Microscale Mg ions also stimulated the expression of osteoinductive molecules in macrophages while Mg ions/macrophage-conditioned medium promoted osteogenesis of BMSCs through the BMP/SMAD signaling pathway. These findings indicate that manipulating Mg ion concentration can endow the Mg biomaterial with favorable osteoimmunomodulatory properties, thereby providing fundamental evidence for improving and modifying the effect of Mg-based bone biomaterials.

Periodontitis is a progressive inflammatory disease initiated by bacterial biofilm adhering to the tooth surface. If left untreated, periodontitis may lead to tooth loss and destruction of the alveolar bone. Regaining the lost alveolar bone is a clinical challenge because of the limited differentiation ability of osteoblasts in inflammatory environments. We have previously shown the anti-inflammatory and antiosteoclastogenic activities of parthenolide (PTL) in human periodontal ligament-derived cells by inhibiting nuclear factor kappa B (NF-κB) signaling, indicating its potential for periodontitis treatment. In this study, we further examined whether PTL could stimulate differentiation of osteoblasts from human alveolar bone in inflammatory conditions and investigated the involvement of the Wnt/β-catenin signaling pathway during this process. The results showed that PTL significantly stimulated alkaline phosphatase activity, mineralization nodule formation, and osteogenesis-related gene/protein expression of osteoblasts under the stimulation of tumor necrosis factor-α (TNF-α). In addition, PTL inhibited the NF-κB/p50 pathway and resisted the inhibition of Wnt/β-catenin signaling induced by TNF-α. Our results indicate that the stimulatory effect of PTL on the differentiation of osteoblasts in inflammatory environments may involve the activation of the Wnt/β-catenin signaling pathway, and PTL may be a promising component for bone regeneration in periodontitis treatment.