No abstract

Compromised autophagy and mitochondrial dysfunction downregulate chondrocytic activity, accelerating the development of osteoarthritis (OA). Irisin, a cleaved form of fibronectin type III domain containing 5 (FNDC5), regulates bone turnover and muscle homeostasis. Little is known about the effect of Irisin on chondrocytes and the development of osteoarthritis. This study revealed that human osteoarthritic articular chondrocytes express decreased level of FNDC5 and autophagosome marker LC3-II but upregulated levels of oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG) and apoptosis. Intra-articular administration of Irisin further alleviated symptoms of medial meniscus destabilization, like cartilage erosion and synovitis, while improved the gait profiles of the injured legs. Irisin treatment upregulated autophagy, 8-OHdG and apoptosis in chondrocytes of the injured cartilage. In vitro, Irisin improved IL-1β-mediated growth inhibition, loss of specific cartilage markers and glycosaminoglycan production by chondrocytes. Irisin also reversed Sirt3 and UCP-1 pathways, thereby improving mitochondrial membrane potential, ATP production, and catalase to attenuated IL-1β-mediated reactive oxygen radical production, mitochondrial fusion, mitophagy, and autophagosome formation. Taken together, FNDC5 loss in chondrocytes is correlated with human knee OA. Irisin repressed inflammation-mediated oxidative stress and extracellular matrix underproduction through retaining mitochondrial biogenesis, dynamics and autophagic program. Our analyses shed new light on the chondroprotective actions of this myokine, and highlight the remedial effects of Irisin on OA development.

Thermotropic properties were characterized by differential scanning calorimetry (Perkin-Elmer DSC-7) in conjunction with hot-stage polarizing optical microscopy (DMLM, Leica; FP90 central processor and F82 hot stage, Mettler Toledo). Optically flat glass substrates used in this study included CaF 2 (Almaz Optics, 1 inch diameter (1 inch » 2.5 cm) and 0.125 inch thick, transparent down to 200 nm), and Schott optical glass FK5 (n = 1.4828 at 780 nm, transparent above 320 nm) and SF57 (n = 1.8258 at 780 nm, transparent above 400 nm), both 1 inch diameter and 0.177 inch thick with nearly matched thermal expansion coefficients, 10.0 10 ±6 and 9.2 10 ±6 K ±1 from 20 to 300 C for FK5 and SF57, respectively. All three types of glass substrate were coated with a polyimide layer and then uniaxially buffed for the preparation of glassy nematic films with their thickness controlled by glass fiber spacers (Bangs Laboratory). The light absorption and linear dichroism were characterized using a UV-vis-NIR spectrophotometer (Lambda 900, Perkin-Elmer), and infrared dichroism using a FTIR spectrometer (Nicolet 20 SXC). An AbbØ refractometer (Bellingham and Stanley, Model 60/HR) was used for the measurement of n e and n o with a 780 nm laser (LiCONiX Diolite 800, 6.0±8.0 mW). A solid sample of II was heated to 250 C and then cooled at a rate of ±20 C/min to room temperature for X-ray diffraction using a Rigaku Bragg-Brentano diffractometer equipped with a copper rotating anode and a position sensitive detector. The optics for this instrument were set up to look for a low-angle peak resulting in a narrow X-ray beam irradiating the sample, particularly at higher 2h angles.

A simple process for the fabrication of large-area well-ordered periodic nanopillar arrays have been developed based on a combination of colloidal lithography and etching techniques. Large-area nanopillar arrays have been successfully fabricated by this approach. The lateral dimensions of nanopillars as small as 40 nm and the aspect ratio as high as 7:1 have been achieved. Our results indicate that it is possible to control the size, shape, and height of nanopillar arrays by fine-tuning the etching recipes. These periodic nanopillar arrays can be used as stamps for nanoimprinting lithography and contact printing lithography to produce more complex periodic nanostructures.

Osteoporosis deteriorates bone mass and biomechanical strength, becoming a life-threatening cause to the elderly. MicroRNA is known to regulate tissue remodeling; however, its role in the development of osteoporosis remains elusive. In this study, we uncovered that silencing miR-29a expression decreased mineralized matrix production in osteogenic cells, whereas osteoclast differentiation and pit formation were upregulated in bone marrow macrophages as co-incubated with the osteogenic cells in transwell plates. In vivo, decreased miR-29a expression occurred in ovariectomy-mediated osteoporotic skeletons. Mice overexpressing miR-29a in osteoblasts driven by osteocalcin promoter (miR-29aTg/OCN) displayed higher bone mineral density, trabecular volume and mineral acquisition than wild-type mice. The estrogen deficiency-induced loss of bone mass, trabecular morphometry, mechanical properties, mineral accretion and osteogenesis of bone marrow mesenchymal cells were compromised in miR-29aTg/OCN mice. miR-29a overexpression also attenuated the estrogen loss-mediated excessive osteoclast surface histopathology, osteoclast formation of bone marrow macrophages, receptor activator nuclear factor-κ ligand (RANKL) and C–X–C motif chemokine ligand 12 (CXCL12) expression. Treatment with miR-29a precursor improved the ovariectomy-mediated skeletal deterioration and biomechanical property loss. Mechanistically, miR-29a inhibited RANKL secretion in osteoblasts through binding to 3′-UTR of RANKL. It also suppressed the histone acetyltransferase PCAF-mediated acetylation of lysine 27 in histone 3 (H3K27ac) and decreased the H3K27ac enrichment in CXCL12 promoters. Taken together, miR-29a signaling in osteogenic cells protects bone tissue from osteoporosis through repressing osteoclast regulators RANKL and CXCL12 to reduce osteoclastogenic differentiation. Arrays of analyses shed new light on the miR-29a regulation of crosstalk between osteogenic and osteoclastogenic cells. We also highlight that increasing miR-29a function in osteoblasts is beneficial for bone anabolism to fend off estrogen deficiency-induced excessive osteoclastic resorption and osteoporosis.

Here, we present a fabrication procedure that can produce large-area, size-tunable, periodic silicon nanopillar arrays, using metal templates that are created via nanosphere lithography. The size of the silicon nanopillars can be systematically controlled by an oxidation and etching process. The smallest size of nanopillars fabricated via this method is ∼9 nm, and the area covered with nanopillars is >1 cm2. Using this approach and nanoimprint lithography, it is possible to pattern sub-10-nm metal nanoparticles with a particle density as high as 1 × 109 particles/cm2.

We report a simple approach to actively control the formation of the self-assembled colloidal crystals in the microfluidic networks using a combination of electrocapillary forces and evaporation-induced self-assembly. Using this scheme, we can not only selectively fabricate the colloidal crystals in the desired channels, but we can also build colloidal crystals with different optical properties in different channels or in the same channel.

The free forms of indoxyl sulfate and p-cresol constituted a small portion of their total forms. The presence of RKF affected levels of free and total indoxyl sulfate. IL-6 level was significantly associated with free indoxyl sulfate level. There was a close relationship between indoxyl sulfate and p-cresol levels in their free forms in PD patients.