Impaired osteoblast function is involved in osteoporosis, and microRNA (miRNA) dysregulation may cause abnormal osteoblast osteogenic activity. However, the influence of miRNA on osteoblast activity and the underlying mechanisms remain elusive. In this study, miR‐103‐3p was found to be negatively correlated with bone formation in bone specimens from elderly women with fractures and ovariectomized (OVX) mice. Additionally, miR‐103‐3p directly targeted Mettl14 to inhibit osteoblast activity, and METTL14‐dependent N⁶‐methyladenosine (m⁶A) methylation inhibited miR‐103‐3p processing by the microprocessor protein DGCR8 and promoted osteoblast activity. Moreover, miR‐103‐3p inhibited bone formation in vivo, and therapeutic inhibition of miR‐103‐3p counteracted the decreased bone formation in OVX mice. Further, METTL14 was negatively correlated with miR‐103‐3p but positively correlated with bone formation in bone specimens from elderly women with fractures and OVX mice. Collectively, our results highlight the critical roles of the miR‐103‐3p/METTL14/m⁶A signaling axis in osteoblast activity, identifying this axis as a potential target for ameliorating osteoporosis.

Wear particle-induced osteoclast over-activation is a major contributor to periprosthetic osteolysis and aseptic loosening, which can cause pathological bone loss and destruction. Hence, inhibiting excessive osteoclast-resorbing activity is an important strategy for preventing periprosthetic osteolysis. Formononetin (FMN) has been shown to have protective effects against osteoporosis, but no previous study has evaluated the effects of FMN on wear particle-induced osteolysis. In this study, we found that FMN alleviated CoCrMo alloy particles (CoPs)-induced bone loss in vivo and inhibited the formation and bone-resorptive function of osteoclasts in vitro. Moreover, we revealed that FMN exerted inhibitory effects on the expression of osteoclast-specific genes via the classical NF-κB and MAPK signaling pathways in vitro. Collectively, FMN is a potential therapeutic agent for the prevention and treatment of periprosthetic osteolysis and other osteolytic bone diseases.

Impaired osteoblast proliferation plays fundamental roles in microgravity‐induced bone loss, and cell cycle imbalance may result in abnormal osteoblast proliferation. However, whether microgravity exerts an influence on the cell cycle in osteoblasts or what mechanisms may underlie such an effect remains to be fully elucidated. Herein, we confirmed that simulated microgravity inhibits osteoblast proliferation. Then, we investigated the effect of mechanical unloading on the osteoblast cell cycle and found that simulated microgravity arrested the osteoblast cell cycle in the G₂ phase. In addition, our data showed that cell cycle arrest in osteoblasts from simulated microgravity was mainly because of decreased cyclin B1 expression. Furthermore, miR‐181c‐5p directly inhibited cyclin B1 protein translation by binding to a target site in the 3′UTR. Lastly, we demonstrated that inhibition of miR‐181c‐5p partially counteracted cell cycle arrest and decreased the osteoblast proliferation induced by simulated microgravity. In conclusion, our study demonstrates that simulated microgravity inhibits cell proliferation and induces cell cycle arrest in the G₂ phase in primary mouse osteoblasts partially through the miR‐181c‐5p/cyclin B1 pathway. This work may provide a novel mechanism of microgravity‐induced detrimental effects on osteoblasts and offer a new avenue to further investigate bone loss induced by mechanical unloading.

Background: Clinically, skeletal muscle ischemia/reperfusion injury is a life-threatening syndrome that is often caused by skeletal muscle damage and is characterized by oxidative stress and inflammatory responses. Bilobalide has been found to have antioxidative and anti-inflammatory effects. However, it is unclear whether bilobalide can protect skeletal muscle from ischemia/reperfusion injury.Methods: The effects of bilobalide on ischemia/reperfusion-injured skeletal muscle were investigated by performing hematoxylin and eosin staining and assessing the wet weight/dry weight ratio of muscle tissue. Then, we measured lipid peroxidation, antioxidant activity and inflammatory cytokine levels. Moreover, Western blotting was conducted to examine the protein levels of MAPK/NF-κB pathway members.Results: Bilobalide treatment could protected hind limb skeletal muscle from ischemia/reperfusion injury by alleviating oxidative stress and inflammatory responses via the MAPK/NF-κB pathways.Conclusions: Bilobalide may be a promising drug for I/R-injured muscle tissue. However, the specific mechanisms for the protective effects still need further study.

Traumatic brain injuries (TBI) are the greatest source of death in trauma, and post-traumatic epilepsy (PTE) is one of the common complications of TBI. Oxidative stress and inflammatory responses play an important role in the process of PTE. Many studies have shown that Jujuboside A has powerful antioxidant and anti-inflammatory properties. However, it is not known whether Jujuboside A has an anti-epileptic effect. The influences of Jujuboside A in the experimental FeCl₃-induced model of PTE were tested by estimating the grade of seizures and performing behavioral tests. Following that, we detected oxidative stress indicators and inflammatory factors. Additionally, western blotting was used to test the protein levels of signaling molecules in MAPK pathways. In this study, Jujuboside A was found to have improved the recognition deficiency and epilepsy syndromes in the experimental rat model. Moreover, oxidative stress and inflammatory responses induced by FeCl₃ injection were relieved by Jujuboside A. In addition, Jujuboside A was found to be capable of reducing the increased expression of p-P38 and p-ERK1/2 caused by iron ions. Collectively, our results demonstrated that Jujuboside A exhibits an antiepileptogenic effect by alleviating oxidative stress and inflammatory responses via the p38 and ERK1/2 pathways.