Autophagy modulates osteoarthritis-related gene expression in human chondrocytes.

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-1ß. 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.

Discotic ionic liquid crystals of triphenylene as dispersants for orienting single-walled carbon nanotubes.

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.

Comparison of the clinical outcome of double-bundle, anteromedial single-bundle, and posterolateral single-bundle anterior cruciate ligament reconstruction using hamstring tendon graft with minimum 2-year follow-up.

PURPOSE: The purpose of this study was to obtain more than 2 years' follow-up after surgery to investigate the effect of the difference in rotatory stability based on our previous data on the clinical outcome among 3 groups: double-bundle (DB) reconstruction group, anteromedial (AM) single-bundle reconstruction group, and posterolateral (PL) single-bundle reconstruction group. METHODS: We randomly separated 55 patients with anterior cruciate ligament rupture into 3 groups: 18 in DB group, 18 in AM group, and 19 in PL group. The mean follow-up period is 33.7 months for the DB group, 31.9 months for the AM group, and 33.2 months for the PL group. We evaluated the Lysholm score, Tegner score, anterior laxity with the KT-1000 arthrometer (MEDmetric, San Diego, CA), rotator instability with the pivot-shift test, and muscle strength with knee extensor and flexor isokinetic peak torques at 60°/s. RESULTS: There were no significant differences in postoperative Lysholm score and Tegner score. Anterior stability of the knee, as measured by the KT-1000 arthrometer, was significantly better in the DB group than the PL group (P < .05). The negative rate of the manual pivot-shift test in the DB group was significantly superior to the PL group (P < .05). Muscle strength of the extensor in the DB group was significantly superior to that in the AM group (P < .05), and muscle strength of the flexor in the PL group was significantly inferior to that in both the DB and AM groups (P < .05). Two patients in the PL group had rerupture; however, there was no graft failure in the other groups. CONCLUSIONS: At 2 years' follow-up, patients undergoing DB anterior cruciate ligament reconstruction had greater extension strength than patients receiving an AM single-bundle reconstruction. The DB and AM groups had greater flexion strength than the PL group. The DB and AM groups had a similar rate of negative pivot-shift test results, whereas the PL group had fewer negative pivot-shift test results than the DB group. There were no KT-1000 side-to-side differences between the DB and AM groups, whereas the DB group had better results than the PL group. Overall, the clinical outcome as measured by Lysholm and Tegner scores was not different between groups. LEVEL OF EVIDENCE: Level II, prospective comparative study.

A prospective randomised study of anatomical single-bundle versus double-bundle anterior cruciate ligament reconstruction: quantitative evaluation using an electromagnetic measurement system.

We conducted a prospective randomised study of anatomical single-bundle (A-SB group) versus double-bundle (A-DB group) anterior cruciate ligament (ACL) reconstruction using the hamstrings tendons. Twenty patients with unilateral ACL deficiency were randomised into two groups. We created the bone tunnels at the position of the original insertion of the anteromedial bundle footprint and posterolateral bundle footprint in the A-DB group and at the central position between these two bundles in the A-SB group. All of the patients were tested before ACL reconstruction and one year after surgery. The KT-1000 measurements, isokinetic muscle peak torque and heel-height difference were evaluated and the general knee condition was assessed by Lysholm score. For pre- and postoperative stability assessment, we used the six-degrees-of-freedom of knee kinematic measurement system using an electromagnetic device (the EMS) for quantitative assessment during the Lachman test and the pivot shift test. There were no significant differences in the KT-1000 measurements, isokinetic muscle peak torque, heel-height difference, and Lysholm score at one-year follow-up between these two groups. The EMS data showed there were significant differences in the acceleration of the pivot shift test between the operated knee and the contralateral normal knees in the A-SB group. In conclusion, clinical outcomes were equally good in both groups. However, the EMS data showed the anatomical double-bundle ACL reconstruction tended to be biomechanically superior to the single-bundle reconstruction.

An organogel system can control the stereochemical course of anthracene photodimerization.

A novel photoresponsive organogel with a binary gelator containing 2-anthracenecarboxylic acid shows a high degree of stereochemical control, resulting in head-to-head photocyclodimers exclusively together with significant enantiomeric excess induced by the chiral counterpart of the gelator.

Studies on a new class of organogelator containing 2-anthracenecarboxylic acid: influence of gelator and solvent on stereochemistry of the photodimers.

A new class of binary organogelator (G1, G2 and G3) based on 2-anthracenecarboxylic acid (2Ac), attached noncovalently with the gelator counterpart containing a 3,4,5-tris(n-dodecyloxy)benzoylamide backbone has been developed. Among the three gelators, two (G2 and G3) are chiral containing D-alanine or L-2-phenylglycine moieties, respectively. They can act as efficient gelators of organic solvents with varying polarity depending upon the gelator systems. Gelator G1 even gelates chiral solvents. The photoirradiation of the gel samples produces photocyclodimers having different degrees of stereoselectivity for different systems. Gels with G1 and G2 produce head-to-head (h-h) photodimers as major products, whereas the stereoselectivity is reversed for the gels with G3 producing head-to-tail (h-t) photodimers as major products. Among those, G2/cyclohexane gel shows the highest degree of stereoselectivity, producing only h-h photodimers with some significant amount of chiral induction. Other chiral systems exhibit low to moderate chiral inductions. The gelator G1 can differentiate between the racemic and enantiomerically pure varieties of a solvent by exhibiting different gel melting temperatures (T(gel)). For different gel systems, T(gel) increases in all the cases as a consequence of photoreaction, except for the G2/cyclohexane gel, where a prominent gel-to-sol phase transition can be observed during the photoreaction. Hydrogen-bonding and pi-pi stacking interactions play the principal roles in constructing the gel structure. The morphologies of the gel systems vary between one-dimensional fibrils and a fibrillar network structure. In addition, the influences of the gelator and solvent polarity on the rate of photoreactions, photoproduct distributions as well as gel structures are investigated.

Bilateral double-layered lateral meniscus: a report of two cases.

Only a few cases of double-layered meniscus have been described in the English literature. We report two cases of bilateral double-layered lateral meniscus, where an additional semicircular meniscus was observed over the normal lateral meniscus. One of the patients exhibited a bucket-handle tear with a double-layered meniscus. To our knowledge, this abnormality is extremely rare and the incidence of double layered meniscus with bucket-handle tear has not been previously reported.

Angle-controlled arrangement of single-walled carbon nanotubes solubilised by 8-quinolinol metal chelate derivatives on mica.

We solubilised SWNTs of short length using a mechanochemical high-speed vibration milling (HSVM) through formation of complexes between the SWNTs and chelate complexes; the mixture formed a network structure on mica.

Organogel of an 8-quinolinol platinum(II) chelate derivative and its efficient phosphorescence emission effected by inhibition of dioxygen quenching.

A newly synthesized 8-quinolinol platinum(II) chelate derivative gelates various organic solvents, and the gel formed shows unique thermo- and solvatochromism of visible and phosphorescent colour in response to a sol-gel phase transition and possesses an attractive ability to inhibit dioxygen quenching of excited triplet states.

Novel host-guest organogels as stabilized by the formation of crown-ammonium pseudo-rotaxane complexes.

A dibenzo-24-crown-8 derivative bearing two cholesterol groups is either insoluble in or precipitates from most organic solvents, but its pseudo-rotaxane complex with a diammonium guest acts as a good gelator of aromatic solvents.

Complementary hydrogen-bonding between thymidine-based low molecular-weight gelator and polynucleotide in organic media.

We have found that aggregation mode and gelation property of thymidine-based organogelator are affected by the addition of its complementary polynucleotide in organic media.

Manipulation of discrete nanostructures by selective modulation of noncovalent forces.

Covalent organic synthesis commonly uses the strategy of selective bond cleavage and formation. If 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.

Autogenous osteochondral graft transplantation for steroid-induced osteonecrosis of the femoral condyle: A report of three young patients.

Steroid-induced osteonecrosis of the femoral condyle is a relatively uncommon condition and is often difficult to select appropriate treatment especially in young patients. Three young men (aged 25, 18, and 24) presented with severe pain and dysfunction of the knee diagnosed as steroid-induced osteonecrosis of the femoral condyle by magnetic resonance imaging (MRIs). Full-thickness cartilage defects sized 20 × 10, 15 × 10, and 30 × 20 mm respectively were classified as International Cartilage Repair Society Grade IV lesions and treated with osteochondral autograft transplantation. They were treated successfully with osteochondral autograft transplantation certificated by post-operative MRI and second look arthroscopy.

Spontaneous formation of dye-functionalized gold nanoparticles using reverse micellar systems.

Detailed exploratory and mechanistic investigations on spontaneous formation of dye-functionalized gold nanoparticles (GNPs) using dye-based reverse micellar systems are described in this publication. The accumulated results from spectroscopic and microscopic investigations demonstrated that water molecules confined within nanoscopic enclosure of the self-assembled reverse micelles played critical role in the redox processes of aurate ions to produce GNPs, which are assumed to have approximately constant size distributions. The resulting dye-functionalized GNPs were found to offer their absorption and fluorescence emission tunability by changing the medium polarity as well as to exhibit excellent film-forming properties to give optically homogeneous polystyrene thin films. These key findings in addition to broad applicability of the self-assembling process with a variety of dye analogues have led to a conclusion that the protocol presented here serves as a versatile synthetic method to provide a potential convenience for future development of new organic-inorganic hybrid nanomaterials.

Potential involvement of SIRT1 in the pathogenesis of osteoarthritis through the modulation of chondrocyte gene expressions.

SIRT1 has been implicated as a key factor in aging-related diseases. Nevertheless, the role of SIRT1 in the pathogenesis of osteoarthritis (OA) is still unknown. We examined the expression of SIRT1 in cartilage samples and the effect of SIRT1 inhibition on chondrocyte gene expression changes to elucidate the role of SIRT1 in chondrocytes. SIRT1 expression was examined using cartilage samples from patients undergoing total knee arthroplasty and femoral head replacement by immunohistochemistry. The effect of SIRT1 inhibition by siRNA on chondrocyte gene expression was examined by real-time PCR and Western blotting. SIRT1 expression was barely detectable in the severely degenerated cartilage while SIRT1 was clearly expressed in the less damaged cartilage. The inhibition of SIRT1 by siRNA induced OA-like gene expression changes, namely the significant down-regulation of aggrecan and up-regulation of COL10A1 and ADAMTS-5. Our observations suggest that SIRT1 expression decreases with development of OA and the reduction of SIRT1 in chondrocytes may cause chondrocyte hypertrophy and cartilage matrix loss. SIRT1 might play important roles in the pathogenesis of OA.