Objective
Autophagy, an evolutionarily conserved process for the bulk degradation of cytoplasmic components, serves as a cell survival mechanism. The purpose of this study was to elucidate the role ...of autophagy in human chondrocytes and pathophysiology of osteoarthritis (OA).
Methods
Autophagy in articular cartilage and primary chondrocytes was assessed using antibodies for the autophagy markers light chain 3 and beclin 1. The states of autophagy under catabolic and nutritional stresses were examined. We also examined the effects of inhibition or induction of autophagy under stimulation with interleukin‐1β. Autophagy was inhibited by small interfering RNA targeting ATG5, and autophagy was induced by rapamycin. The effects of inhibition or induction of autophagy were examined by real‐time polymerase chain reaction for aggrecan, COL2A1, MMP13, and ADAMTS5 messenger RNA. To further examine the mechanism of autophagy regulation in OA human chondrocytes, we investigated whether autophagy modulates apoptosis and reactive oxygen species (ROS).
Results
Autophagy was increased in OA chondrocytes and cartilage. Catabolic and nutritional stresses increased autophagy. In addition, the inhibition of autophagy caused OA‐like gene expression changes, while the induction of autophagy prevented them. Furthermore, the inhibition of autophagy increased the amount of cleaved poly(ADP‐ribose) polymerase and cleaved caspase 9, while the induction of autophagy inhibited these increases. ROS activity was also decreased by induction of autophagy.
Conclusion
These observations suggested that increased autophagy is an adaptive response to protect cells from stresses, and that autophagy regulates OA‐like gene expression changes through the modulation of apoptosis and ROS. Further studies about autophagy in chondrocytes will provide novel insights into the pathophysiology of OA.
Covalent organic synthesis commonly uses the strategy of selective bond cleavage and formation. It a similar approach can be applied stepwisely to noncovalent synthesis, more exotic or challenging ...nanostructures might become achievable. Here, we report that ferrocene-based tetratopic pyridyl ligands, which can dynamically change their geometry by means of thermal rotation of their cyclopentadienyl rings in solution, assemble with AgBF4 into discrete metal-organic nanotubes with large and uniform diameters. The nanotubes can be cut into metal-organic nanorings through selective attenuation of the inter-nanoring interaction via ferrocene oxidation. The resultant nanorings can be transferred onto inorganic substrates electrostatically or allowed to reassemble to form the original nanotube by the reductive neutralization of their oxidized ferrocene units.
Boronic Acids in Molecular Self-Assembly Fujita, Norifumi; Shinkai, Seiji; James, Tony D.
Chemistry, an Asian journal,
July 7, 2008, Letnik:
3, Številka:
7
Journal Article
Recenzirano
The reversibility of boronic acid and diol interaction makes it an ideal candidate for the design of self‐assembled molecular structures. Reversibility is required to ensure that the ...thermodynamically most stable structure is formed. Reversibility also ensures that any errors produced during the assembly process are not permanent.
It works both ways: The reversible interaction of boronic acids with diols to generate self‐assembled structures is an emerging area in organic material science with applications in gas storage, catalysis, and separation. Reversibility is required to ensure that the thermodynamically most stable structure is formed.
Say cheeeese! The thixotropic processes that occur in a naphthalenediimide‐based organogel can be imaged in real time by TEM and AFM (see picture). The self‐assembled 1D fibers disintegrate under ...mechanical stress and undergo a self‐healing process during a resting time to reconstitute the 1D fibers.
Like a color palette: A naphthalenediimide‐based organogel colorimetric sensor allows recognition of the positional isomers of dihydroxynaphthalene in the gel phase with the naked eye. Intercalation ...of the dihydroxynaphthalene into the gel matrix produces a donor–acceptor interaction, which gives the gel a distinct color that depends on the strength of noncovalent (H‐bonding, π‐stacking, van der Waals) interactions.
Orient and conduct: Triphenylene‐based discotic ionic liquid crystals (ILCs) with six imidazolium ion pendants can disperse pristine single‐walled carbon nanotubes (SWNTs). When the ILC is columnarly ...assembled, doping with SWNTs results in macroscopic homeotropic columnar orientation. Combination of shear and annealing treatments gives rise to three different orientation states, which determine the anisotropy of electrical conduction.
A series of quater‐, quinque‐, and sexithiophene derivatives bearing two cholesteryl groups at the α‐position, which are abbreviated as 4 T‐(chol)2, 5 T‐(chol)2, and 6 T‐(chol)2, respectively, have ...been synthesized. It has been found that these oligothiophene derivatives act as excellent organogelators for various organic fluids and show the unique thermochromic behaviors through the sol–gel phase transition. It was shown on the basis of extensive investigations, performed with UV‐visible spectroscopy, circular dichroism (CD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM), that these gelators self‐assemble into the one‐dimensional structures in the organogels, in which the π‐block moieties of the oligothiophenes are stacked in an H‐aggregation mode. Surprisingly, an AFM image shows that 4 T‐(chol)2 forms unimolecular fibers in a left‐handed helical sense, whereby one pitch of the helical fiber is constructed by 400–540 4 T‐(chol)2 molecules. Very interestingly, the conformational change in the oligothiophene moieties can be visually detected: for example, 6 T‐(chol)2 shows a specific absorption maximum in the gel (λmax=389 nm) and in the solution (λmax=439 nm). In addition, a sol–gel phase transition of the 6 T‐(chol)2 gel was implemented by addition of oxidizing and reducing reagents such as FeCl3 and ascorbic acid, respectively. The stimuli‐responsive functionality of the oligothiophene‐based organogels makes them promising candidates for switchable opto‐ and electronic soft materials.
Novel thermochromic organogels bearing oligothiophene backbones were prepared under the concept of the controllable conjugation length accompanied with one‐dimensinal self‐assembling. The phase transition is illustrated here.
A prismlike hollow structure was assembled when three pyridyl‐substituted porphyrin panels were linked by six PdII ions. A dramatic D3h→C2 structural change of the prism (see scheme) was triggered by ...complexation of pyrene.
