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Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement. However, the key regulatory molecules involved in osteoclastogenesis during this process remain unclear. Long noncoding RNAs (lncRNAs) are a newly identified class of functional RNAs that regulate cellular processes, such as gene expression and translation regulation. Recently, lncRNAs have been reported to be involved in osteogenesis and bone formation. However, as the most abundant noncoding RNAs in vivo, the potential regulatory role of lncRNAs in osteoclast formation and bone resorption urgently needs to be clarified. We recently found that the lncRNA Nron (long noncoding RNA repressor of the nuclear factor of activated T cells) is highly expressed in osteoclast precursors. Nron is downregulated during osteoclastogenesis and bone ageing. To further determine whether Nron regulates osteoclast activity during orthodontic treatment, osteoclastic Nron transgenic (Nron cTG) and osteoclastic knockout (Nron CKO) mouse models were generated. When Nron was overexpressed, the orthodontic tooth movement rate was reduced. In addition, the number of osteoclasts decreased, and the activity of osteoclasts was inhibited. Mechanistically, Nron controlled the maturation of osteoclasts by regulating NFATc1 nuclear translocation. In contrast, by deleting Nron specifically in osteoclasts, tooth movement speed increased in Nron CKO mice. These results indicate that lncRNAs could be potential targets to regulate osteoclastogenesis and orthodontic tooth movement speed in the clinic in the future.
Assuntos
Animais , Camundongos , Reabsorção Óssea , Genética , Camundongos Endogâmicos C57BL , Osteoclastos , Osteogênese , Ligante RANK , RNA Longo não Codificante , GenéticaRESUMO
Unlike adult mammalian heart, zebrafish heart has a remarkable capacity to regenerate after injury. Previous study has shown Notch signaling activation in the endocardium is essential for regeneration of the myocardium and this activation is mediated by hemodynamic alteration after injury, however, the molecular mechanism has not been fully explored. In this study we demonstrated that blood flow change could be perceived and transmitted in a primary cilia dependent manner to control the hemodynamic responsive klf2 gene expression and subsequent activation of Notch signaling in the endocardium. First we showed that both homologues of human gene KLF2 in zebrafish, klf2a and klf2b, could respond to hemodynamic alteration and both were required for Notch signaling activation and heart regeneration. Further experiments indicated that the upregulation of klf2 gene expression was mediated by endocardial primary cilia. Overall, our findings reveal a novel aspect of mechanical shear stress signal in activating Notch pathway and regulating cardiac regeneration.
RESUMO
Unlike adult mammalian heart, zebrafish heart has a remarkable capacity to regenerate after injury. Previous study has shown Notch signaling activation in the endocardium is essential for regeneration of the myocardium and this activation is mediated by hemodynamic alteration after injury, however, the molecular mechanism has not been fully explored. In this study we demonstrated that blood flow change could be perceived and transmitted in a primary cilia dependent manner to control the hemodynamic responsive klf2 gene expression and subsequent activation of Notch signaling in the endocardium. First we showed that both homologues of human gene KLF2 in zebrafish, klf2a and klf2b, could respond to hemodynamic alteration and both were required for Notch signaling activation and heart regeneration. Further experiments indicated that the upregulation of klf2 gene expression was mediated by endocardial primary cilia. Overall, our findings reveal a novel aspect of mechanical shear stress signal in activating Notch pathway and regulating cardiac regeneration.
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Fractures are frequently occurring diseases that endanger human health. Crucial to fracture healing is cartilage formation, which provides a bone-regeneration environment. Cartilage consists of both chondrocytes and extracellular matrix (ECM). The ECM of cartilage includes collagens and various types of proteoglycans (PGs), which play important roles in maintaining primary stability in fracture healing. The PG form of dentin matrix protein 1 (DMP1-PG) is involved in maintaining the health of articular cartilage and bone. Our previous data have shown that DMP1-PG is richly expressed in the cartilaginous calluses of fracture sites. However, the possible significant role of DMP1-PG in chondrogenesis and fracture healing is unknown. To further detect the potential role of DMP1-PG in fracture repair, we established a mouse fracture model by using a glycosylation site mutant DMP1 mouse (S89G-DMP1 mouse). Upon inspection, fewer cartilaginous calluses and down-regulated expression levels of chondrogenesis genes were observed in the fracture sites of S89G-DMP1 mice. Given the deficiency of DMP1-PG, the impaired IL-6/JAK/STAT signaling pathway was observed to affect the chondrogenesis of fracture healing. Overall, these results suggest that DMP1-PG is an indispensable proteoglycan in chondrogenesis during fracture healing.
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Objective To evaluate the relationship between plasma substance P (SP) and calcitonin gene-related peptide (CGRP) concentrations and intraoperative cardiovascular events in diabetic patients.Methods Twenty-two patients of either sex with type 2 diabetes mellitus and 22 non-diabetic patients of either sex,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,aged 50-77 yr,undergoing elective knee arthroplasty under neuraxial anesthesia,served as diabetes mellitus group (group DM) and non-diabetes mellitus group (group NDM),respectively.The patients of either group were further divided into 2 subgroups (n =11 each) according to whether or not the patients had cardiovascular diseases before operation:no cardiovascular disease subgroups (NDM-NCVD subgroup and DM-NCVD subgroup) and cardiovascular disease subgroups (NDM-CVD subgroup and DM-CVD subgroup).The plasma SP and CGRP concentrations were dertermined by enzyme-linked immunosorbent assay at 30 min before operation and at the end of operation.The plasma cardiac troponin Ⅰ (cTnI) concentrations were measrued by enzyme-linked immunosorbent assay at 30 min before operation and 24 h after operation.The development of intraoperative cardiovascular events was recorded.Results Compared with group NDM,the incidence of intraoperative cardiovascular events and plasma cTnI concentrations at each time point were significantly increased,and the plasma concentrations of SP and CGRP were decreased in group DM (P＜0.05).Compared with group DM-NCVD,the incidence of intraoperative cardiovascular events and plasma cTnI concen trations at each time point were significantly increased,and the plasma concentrations of SP and CGRP were decreased in group DM-CVD (P＜0.05).Conclusion The development of intraoperative cardiovascular events is related to the decrease in plasma concentrations of SP and CGRP in diabetic patients.
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@#M-waves and F-responses were investigated before and after massage using the bipolar surface electrodes to stimulate the tibial nerve at the ankle recorded by bipolar surface electrodes from the muscle flexor hallucis in 30 children with cerebral palsy. After treatment, the amplitudes of the M-wave increased (P＜0.05 ); F-response reduced (P＜0.05 )in the lesion side. The observations were made bilaterally and the results revealed no significant differences(P＞0.05 )by comparing side to side. The latencies of Mwaves prolonged to 6.09～8. 28ms(P<0.05);F-responses 29.07～3l. 42ms(only Fn wave was P＜0.05in the lesion side). The significant efficiency was 25.93 %,the efficiency was 88.89 % except that 2 objects did not change and one continued to deteriorate. The experimental results suggest that the massage can improve the functional disorder of the skeletal muscle and the ventral horn of the spinal cord.
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AIM: To evaluate the therapeutic effect and safety of Rhadiola Extract Injection for treatment of stable angina pectoris of coronary heart disease with cariac blood stasis syndrome. METHODS: Arandomized,double-blind,positive drug parallel controlled,multi-center clinical trial was adopted.414 patients with stable angna pectoris of coronary heart disease with cariac blood stasis syndrome were randomly chosen and divided into two groups: test group(n=308 cases) and control group(n=106 cases).The test group was treated with Rhadiola Extract Injection and the control group received Xiangdan Injection.Treatment course of each group was 10 days.(RESULTS:) The therapeutic effect and changes of electrocardiogram in the test group were better than that of the control group(P0.05).The test group had no obvious side-effects. CONCLUSION: Rhadiola Extract Injection is safe and effective in treating stable angina pectoris of coronary heart disease with cariac blood stasis syndrome.