Exosomes-the enigmatic regulators of bone homeostasis

Exosomes are a heterogeneous group of cell-derived membranous structures, which mediate crosstalk interaction between cells.Recent studies have revealed a close relationship between exosomes and bone homeostasis. It is suggested that bone cells can spontaneously secret exosomes containing proteins, lipids and nucleic acids, which then to regulate osteoclastogenesis and osteogenesis. However, the network of regulatory activities of exosomes in bone homeostasis as well as their therapeutic potential in bone injury remain largely unknown. This review will detail and discuss the characteristics of exosomes, the regulatory activities of exosomes in bone homeostasis as well as the clinical potential of exosomes in bone injury.

METTL3-mediated m^(6)A RNA methylation regulates dorsal lingual epithelium homeostasis

The dorsal lingual epithelium,which is composed of taste buds and keratinocytes differentiated from K14^(+)basal cells,discriminates taste compounds and maintains the epithelial barrier.N6-methyladenosine(m^(6)A)is the most abundant mRNA modification in eukaryotic cells.How METTL3-mediated m^(6)A modification regulates K14^(+)basal cell fate during dorsal lingual epithelium formation and regeneration remains unclear.Here we show knockout of Mettl3 in K14^(+)cells reduced the taste buds and enhanced keratinocytes.Deletion of Mettl3 led to increased basal cell proliferation and decreased cell division in taste buds.Conditional Mettl3 knock-in mice showed little impact on taste buds or keratinization,but displayed increased proliferation of cells around taste buds in a protective manner during post-irradiation recovery.Mechanically,we revealed that the most frequent m^(6)A modifications were enriched in Hippo and Wnt signaling,and specific peaks were observed near the stop codons of Lats1 and FZD7.Our study elucidates that METTL3 is essential for taste bud formation and could promote the quantity recovery of taste bud after radiation.

Invariance and Noises of Shannon Entropy for Information on Oxidative Activity of DNA in All Living Cells for Medical Diagnostics

We analyze oxidative activity of DNA due to fluorescence of chromosomes inside cells, using flow cytometry method with nanometer spatial resolution. Statistics of fluorescence is presented in histogram as frequency distributions of flashes in the dependence on their intensity and in distributions of Shannon entropy, which was defined on the base of normalized distribution of information in original histogram for frequency of flashes. We show that overall sum of entropy, i.e. total entropy E , for any histogram is invariant and has identical trends of changes all values of E(r) = lnr at reduction of histogram’ rank r. This invariance reflects informational homeostasis of chromosomes activity in multi-scale networks of entropy inside all cells in various samples of blood for DNA inside neutrophils, lymphocytes, inside all leukocytes of human and inside chicken erythrocytes for various dyes, colors and various excitations of fluorescence. Informational homeostasis of oxidative activity of 3D DNA in the full set of chromosomes inside living cells exists for any Shannon-Weaver index of biodiversity of cells, at any state of health different beings. Regulation perturbations in information activity DNA provides informational adaptability and vitality of cells at homeostasis support. Noises of entropy, during regulation of informational homeostasis, depend on the states of health in real time. The main structural reconstructions of chromosomal correlations, corresponding to self-regulation of homeostasis, occur in the most large-scale networks of entropy, for rank r<32. We show that stability of homeostasis is supported by activity of all 46 chromosomes inside cells. Patterns, hidden switching and branching in sequences of averages of H?lder and central moments for noises in regulation of homeostasis define new opportunities in diagnostics of health and immunity. All people and all aerobic beings have one overall homeostatic level for countdown of information activity of DNA inside cells. We noted very bad and dangerous properties of artificial cells with other levels of informational homeostasis for all aerobic beings in foods, medical treatment and in biotechnologies.

The Hedgehog signalling pathway in bone formation

The Hedgehog（Hh） signalling pathway plays many important roles in development,homeostasis and tumorigenesis.The critical function of Hh signalling in bone formation has been identified in the past two decades.Here,we review the evolutionariiy conserved Hh signalling mechanisms with an emphasis on the functions of the Hh signalling pathway in bone development,homeostasis and diseases.In the early stages of embryonic limb development,Sonic Hedgehog（Shh） acts as a major morphogen in patterning the limb buds.Indian Hedgehog（Ihh） has an essential function in endochondral ossification and induces osteoblast differentiation in the perichondrium.Hh signalling is also involved intramembrane ossification.Interactions between Hh and Wnt signalling regulate cartilage development,endochondral bone formation and synovial joint formation.Hh also plays an important role in bone homeostasis,and reducing Hh signalling protects against age-related bone loss.Disruption of Hh signalling regulation leads to multiple bone diseases,such as progressive osseous heteroplasia.Therefore,understanding the signalling mechanisms and functions of Hh signalling in bone development,homeostasis and diseases will provide important insights into bone disease prevention,diagnoses and therapeutics.

SMURF2 regulates bone homeostasis by disrupting SMAD3 interaction with vitamin D receptor in osteoblasts

Subject Code:H06 With the support by the National Natural Science Foundation of China,a study by the research group led by Prof.Zou Weiguo(邹卫国)from the Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,CAS demonstrates that E3ligase SMURF2maintains bone