Osteopontin (OPN), a secreted phosphoprotein, is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of cell matrix proteins and participates in many biological activities. Studies have shown that OPN plays a role in bone metabolism and homeostasis. OPN not only is an important factor in neuron-mediated and endocrine-regulated bone mass, but also is involved in biological activities such as proliferation, migration, and adhesion of several bone-related cells, including bone marrow mesenchymal stem cells, hematopoietic stem cells, osteoclasts, and osteoblasts. OPN has been demonstrated to be closely related to the occurrence and development of many bone-related diseases, such as osteoporosis, rheumatoid arthritis, and osteosarcoma. As expected, the functions of OPN in the bone have become a research hotspot. In this article, we try to decipher the mechanism of OPN-regulated bone metabolism and bone diseases.

Background and Purpose: Melatonin is a neurohormone involved in bone homeostasis. Melatonin directs bone remodelling and the role of bone marrow mesenchymal stem cells (BMMSCs) in the regulating melatonin‐mediated bone formation–resorption balance remains undefined.Experimental Approach: Osteoporosis models were established and bone tissue and serum were collected to test the effects of melatonin on bone homeostasis. Melatonin receptors were knocked down, the NF‐κB signalling pathway and receptor activator of NF‐κB ligand (RANKL) expression were investigated. Communication between bone marrow mesenchymal stem cells and osteoclasts was detected with direct‐contact or indirect‐contact system.Key Results: Bone loss and microstructure disorder in mice were reversed after melatonin treatment, as a result of anabolic and anti‐resorptive effects. In vitro, a physiological (low) concentration of melatonin promoted the bone marrow mesenchymal stem cells, osteogenic lineage commitment and extracellular mineralization but had no impact on extracellular matrix synthesis. After MT knockdown, especially MT₂, the positive effects of melatonin on osteogenesis were attenuated. The canonical NF‐κB signalling pathway was the first discovered downstream signalling pathway after MT receptor activation and was found to be down‐regulated by melatonin during osteogenesis. Melatonin suppressed BMMSC‐mediated osteoclastogenesis by inhibiting RANKL production in BMMSCs and this effect only occurred when BMMSCs and osteoclast precursors were co‐cultured in an indirect‐contact manner.Conclusion and Implications: Our work suggests that melatonin plays a crucial role in bone balance, significantly accelerates the osteogenic differentiation of bone marrow mesenchymal stem cells by suppressing the MT₂‐dependent NF‐κB signalling pathway, and down‐regulates osteoclastogenesis via RANKL paracrine secretion.

Background: When a tooth is diagnosed with irreversible pulpitis, root canal therapy (RCT) is generally performed to completely remove pulp tissue, which might lead to a higher risk of loss of vascularity, and teeth being more prone to fracture. Vital pulp therapy (VPT) is a personalized method of treating irreversible pulpitis, which conforms to the trend of minimally invasive endodontics. The remaining vital pulp could promote the physiological development of the roots of young permanent teeth with incomplete apical foramen. However, clear guidelines for VPT indication are still missing. Objective: This prospective cohort study evaluated the outcomes of vital pulp therapy (VPT) using iRoot BP Plus (Innovative Bioceramix Inc, Vancouver, BC, Canada) in permanent teeth of 6- to 20-year-old patients with irreversible pulpitis caused by caries and analyzed the preoperative factors affecting VPT prognosis. Methods: Fifty-nine permanent teeth in 59 patients with irreversible pulpitis caused by caries were treated with VPT using iRoot BP Plus. All patients received VPT under a standardized protocol. After informed consent, teeth were isolated with a dental dam, then operators performed VPT with iRoot BP Plus and restored the teeth with composite resin or stainless steel crown. Patients were postoperatively recalled after 3, 6 and 12 months and then recalled annually. Successful cases were defined as successful in both clinical and radiographic evaluations. A statistical analysis was performed using the Fisher exact test, and the level of significant difference was p < 0.05. Results: After 6–36 months of follow-up, a total of 57 teeth from 57 patients were accessible for evaluation. The mean age of subjects was 11.75 ± 3.81 years. The overall clinical and radiographic success rate of VPT was 91.2% (52/57). With an observation time of one year or more, the success rate was 90.5% (38/42). All the symptoms and physical examination findings showed no significant effect on VPT prognosis (p > 0.05) using a binary logistic regression model. Conclusions: Permanent teeth in 6- to 20-year-old patients diagnosed as irreversible pulpitis caused by caries can be successfully treated with VPT using iRoot BP Plus.

Nanoparticles, presenting catalytic activity to induce intracellular oxidative species, have been extensively explored for tumor treatment, but suffer daunting challenges in the limited intracellular H₂O₂ and thus suppressed therapeutic efficacy. Here in this study, a type of composite nanoparticles, consisting CaO₂ core and Co-ferrocene shell, is designed and synthesized for combinational tumor treatment. The findings indicate that CaO₂ core can be hydrolyzed to produce large amounts of H₂O₂ and calcium ions at the acidic tumor sites. Meanwhile, Co-ferrocene shell acts as an excellent Fenton catalyst, inducing considerable ROS generation following its reaction with H₂O₂. Excessive cellular oxidative stress triggers agitated calcium accumulation in addition to the calcium ions released from the particles. The combined effect of intracellular ROS and calcium overload causes significant tumor inhibition both in vitro and in vivo.