Excess osteoclast activity is found in many bone metabolic diseases, and inhibiting osteoclast differentiation has proven to be an effective strategy. Here, we revealed that osteoclast precursors (pre-OCs) were more susceptible to thioredoxin reductase 1 (TXNRD1) inhibitors than bone marrow-derived monocytes (BMDMs) during receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclastogenesis. Mechanistically, we found that nuclear factor of activated T-cells 1 (NFATc1) upregulated solute carrier family 7 member 11 (SLC7A11) expression through transcriptional regulation during RANKL-induced osteoclastogenesis. During TXNRD1 inhibition, the rate of intracellular disulfide reduction is significantly reduced. Increased cystine transport leads to increased cystine accumulation, which leads to increased cellular disulfide stress and disulfidptosis. We further demonstrated that SLC7A11 inhibitors and treatments that prevent disulphide accumulation could rescue this type of cell death, but not the ferroptosis inhibitors (DFO, Ferro-1), the ROS scavengers (Trolox, Tempol), the apoptosis inhibitor (Z-VAD), the necroptosis inhibitor (Nec-1), or the autophagy inhibitor (CQ). An in vivo study indicated that TXNRD1 inhibitors increased bone cystine content, reduced the number of osteoclasts, and alleviated bone loss in an ovariectomized (OVX) mouse model. Together, our findings demonstrate that NFATc1-mediated upregulation of SLC7A11 induces targetable metabolic sensitivity to TXNRD1 inhibitors during osteoclast differentiation. Moreover, we innovatively suggest that TXNRD1 inhibitors, a classic drug for osteoclast-related diseases, selectively kill pre-OCs by inducing intracellular cystine accumulation and subsequent disulfidptosis.

Nanofiber mats have been widely applied in various biomedical fields such as drug delivery, tissue repair and wound dressing. In this study, the curcumin-loaded mesoporous silica incorporated nanofiber mats were prepared using blend electrospinning of curcumin-loaded mesoporous silica nanoparticles (CCM-MSNs) and polyvinyl pyrrolidone (PVP) for hemostasis. The prepared mats were then evaluated to determine their structure, biocompatibility and antibacterial activity, especially focusing on the hemostatic effect using an in vivo liver injury model. The results showed that CCM-MSN loading ratios less than 8 wt% could be homogeneously dispersed in the PVP electrospun nanofibers. The in vitro studies demonstrated that the hybrid nanofiber mats had no obvious toxic effect on the growth of L929 cells. The hybrid nanofiber mats also exhibited enhanced in vitro antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA). The antibacterial effect of the hybrid nanofiber mats was further confirmed by in vivo experiments. Moreover, the in vivo hemostasis studies revealed that the hybrid nanofiber mats could rapidly transform into hydrogel when they contact with blood, and then activate the clotting system to stop the wound bleeding. Therefore, the CCM-MSN incorporated PVP nanofiber mats provide a practical possibility for nanofiber-based hemostatic materials with good biocompatibility and high antibacterial activity.

Objectives: Intracellular reactive oxygen species (ROS) induced by receptor activator of NF‐kB ligand (RANKL) has been proven to be a critical factor in the development of osteoclasts. This study aimed to prove that schisandrin A (Sch), a novel anti‐oxidant compound, is able to suppress osteoclastogenesis and prevent bone loss in ovariectomized (OVX) mice by suppressing ROS via nuclear factor erythroid 2‐related factor (Nrf2).Material and Methods: Micro‐CT was used to detect bone formation. The effects of Sch on receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced reactive oxygen species (ROS) were measured by dihydroethidium (DHE) staining in vivo and 2',7'‐dichlorodihydrofluorescein diacetate (DCFH‐DA) staining in vitro. Immunofluorescence staining was used to detect the expression of Nrf2 in vivo. siRNA was used to evaluate the effect of Nrf2 in osteoclastogenesis.Results: Sch suppresses RANKL‐induced ROS production by regulating nuclear factor erythroid 2‐related factor (Nrf2) in vitro and vivo. Mechanistically, Sch enhances the expression of Nrf2 by regulating the degradation of Nrf2. Further, Sch suppresses phosphorylation of P65 and its nuclear translocation, as well as the degradation of IκBα. Collectively, our findings reveal that Sch protects against OVX‐induced bone loss by suppressing ROS via Nrf2.Conclusions: Our results showed the potential of anti‐oxidant compound schisandrin A in the treatment of osteoporosis, highlighting Nrf2 as a novel promising target in osteoclast‐related disease.

Pearl/calcium sulfate (pearl/CaSO ₄ ) composite scaffolds were successfully fabricated by 3D printing with a hydration process, and showed enhanced physicochemical and biological properties for bone regeneration.

The biomaterials’ success within the tissue engineering field is hinged on the capability to regulate tissue and cell responses, comprising cellular adhesion, as well as repair and immune processes’ induction. In an attempt to enhance and fulfill these biomaterials’ functions, scholars have been inspired by nature; in this regard, surface modification via coating the biomaterials with polydopamine is one of the most successful inspirations endowing the biomaterials with surface adhesive properties. By employing this approach, favorable results have been achieved in various tissue engineering-related experiments, a significant one of which is the more rapid cellular growth observed on the polydopamine-coated substrates compared to the untreated ones; nonetheless, some considerations regarding polydopamine-coated surfaces should be taken into account to control the ultimate outcomes. In this mini-review, the importance of coatings in the tissue engineering field, the different types of surfaces requiring coatings, the significance of polydopamine coatings, critical factors affecting the result of the coating procedure, and recent investigations concerning applications of polydopamine-coated biomaterials in tissue engineering are thoroughly discussed.