Inhibitory effects of Formononetin on CoCrMo particle-induced osteoclast activation and bone loss through downregulating NF-κB and MAPK signaling.

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.

Osteogenic potential evaluation of biotin combined with magnesium-doped hydroxyapatite sustained-release film.

Biotin is one of the water-soluble B-complex group of vitamins. Recent studies have found that the relative protein expression of BMP2, BSP and OPG in MC3T3-E1 cells is prominent after 14 days of co-culture with biotin film, especially for BMP2. It is also found that the rapid degradation of biotin film in vivo limits its application value. In this work, magnesium-doped hydroxyapatite (MgHA) film can form a porous network structure as a biological sustained-release film. Therefore, the multilayer (MgHA|biotin|MgHA|biotin) film was prepared by pulsed laser assisted electron beam deposition technique. The morphology, structure and properties of biotin film and multilayer film were analyzed and characterized. Also, the osteogenic effect of biotin film and multilayer film was evaluated after implantation into the femoral bone marrow cavity of SD rats. The results of micro-CT scan and 3D reconstruction showed that there were a large number of trabecular bones around the multilayer film, which was superior to biotin film in osteogenesis. Hematoxylin-eosin staining showed cancellous bone structure and intact bone marrow structure around the multilayer film, and the newly formed bone became lamellar. Masson-trichromatic staining revealed abundant osteoid and braided bone formation around the multilayer film. In conclusion, MgHA sustained release film can realize the continuous release of bioactive drugs, which provides a new route to accelerate the repair of bone defects.

MiR-103-3p targets the m6 A methyltransferase METTL14 to inhibit osteoblastic bone formation.

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 (m6 A) 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/m6 A signaling axis in osteoblast activity, identifying this axis as a potential target for ameliorating osteoporosis.

[Diagnosis and treatment of Charcot's osteoarthropathy].

Charcot foot is a rare disease in clinic, its pathogenesis includes neurotrauma theory, neurovascular theory, comprehensive theory, and inflammatory factor theory. The disease is characterized by progressive joint and bone destruction of foot and ankle joint. Conventional X-ray examination is not sensitive to the early diagnosis of disease, the manifestation of CT and MRI of disease is characteristic and could be used to make a comprehensive evaluation of bone and soft tissue lesions of disease. It is not difficult to make a diagnosis based on characteristic findings of CT and MRI and clinical manifestations such as swelling, pain and skin temperature rising of foot and ankle. Charcot foot has multiple classification methods including anatomy, imaging and clinical classification. Improved Eichenholtz staging classification is most commonly used currently which could make a more comprehensive assessment of disease and guide treatment better. According to the stage of disease, treatment could be carried out including non-weight bearing and brace protection, drugs therapy and surgical treatment, etc. Early diagnosis, brace protection, could protect joint and delaying progression of deformity. There is no clear long-term and generally accepted conclusion about the efficacy of drug therapy. For advanced patients, surgical treatment must be actively performed to preserve a stable and functional ankle joint and reduce amputation rate.