RANKL expression in chondrocytes and its promotion by lymphotoxin-alpha in the course of cartilage destruction during rheumatoid arthritis

We investigated the expression and localization of the receptor activator nuclear factor kappa B ligand (RANKL) in cartilage from patients with rheumatoid arthritis (RA) of relevance to cartilage degeneration. We also examined the role of exogenous lymphotoxin (LT)-alpha on RANKL expression in human chondrocytes and its effect on in vitro osteoclast differentiation. Cartilage and synovial fluid samples were obtained from 45 patients undergoing total joint replacement surgery or joint puncture, including 24 patients with osteoarthritis (OA) and 21 patients with RA. RANKL expression in articular cartilage was examined by immunohistochemistry. LT-alpha concentrations in synovial fluid were measured using an enzyme-linked immunosorbent assay (ELISA). Normal human chondrocytes were stimulated with LT-alpha, and the relative mRNA levels of RANKL, osteoprotegerin (OPG), matrix metalloproteinase-9, and vascular endothelial growth factor were examined by real-time polymerase chain reaction. Soluble RANKL protein in culture media was measured using ELISA, and membrane-bound RANKL protein in cells was examined by western blotting. Co-cultures of human chondrocytes with peripheral blood mononuclear cells (PBMCs) were stimulated with macrophage-colony stimulating factor and LT-alpha, and osteoclast differentiation was evaluated by staining for tartrate-resistant acid phosphatase. LT-alpha concentrations were higher in RA synovial fluid than in OA samples. The population of RANKL-positive chondrocytes of RA cartilage was higher than that of OA cartilage, and correlated with cartilage degeneration. Stimulation of cultured human chondrocytes by LT-alpha increased RANKL expression, the RANKL/OPG ratio, and angiogenic factors. Membrane-bound RANKL in chondrocytes was up-regulated after stimulation of LT-alpha, whereas soluble RANKL in culture medium did not increase. Co-cultures of human chondrocytes and PBMCs demonstrated that LT-alpha stimulated human chondrocytes to produce RANKL and induced osteoclastic differentiation of PBMCs. RANKL produced by chondrocytes may contribute to cartilage destruction during RA and LT-alpha could promote the expression of RANKL in human chondrocytes

Adipose-Derived Extract Suppresses IL-1 beta-Induced Inflammatory Signaling Pathways in Human Chondrocytes and Ameliorates the Cartilage Destruction of Experimental Osteoarthritis in Rats

We investigated the effects of adipose-derived extract (AE) on cultured chondrocytes and in vivo cartilage destruction. AE was prepared from human adipose tissues using a nonenzymatic approach. Cultured human chondrocytes were stimulated with interleukin-1 beta (IL-1 beta) with or without different concentrations of AE. The effects of co-treatment with AE on intracellular signaling pathways and their downstream gene and protein expressions were examined using real-time PCR, Western blotting, and immunofluorescence staining. Rat AE prepared from inguinal adipose tissues was intra-articularly delivered to the knee joints of rats with experimental osteoarthritis (OA), and the effect of AE on cartilage destruction was evaluated histologically. In vitro, co-treatment with IL-1 beta combined with AE reduced activation of the p38 and ERK mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of the p65 subunit of nuclear factor-kappa B (NF-kappa B), and subsequently downregulated the expressions of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, IL-6, and IL-8, whereas it markedly upregulated the expression of IL-1 receptor type 2 (IL-1R2) in chondrocytes. Intra-articular injection of homologous AE significantly ameliorated cartilage destruction six weeks postoperatively in the rat OA model. These results suggested that AE may exert a chondroprotective effect, at least in part, through modulation of the IL-1 beta-induced inflammatory signaling pathway by upregulation of IL-1R2 expression

The surprisingly low carbon mass in the debris disk around HD 32297

Gas has been detected in a number of debris disks. It is likely secondary, i.e. produced by colliding solids. Here, we report ALMA Band 8 observations of neutral carbon in the CO-rich debris disk around the 15--30 Myr old A-type star HD 32297. We find that C$^0$ is located in a ring at $\sim$110 au with a FWHM of $\sim$80 au, and has a mass of $(3.5\pm0.2)\times10^{-3}$ M$_\oplus$. Naively, such a surprisingly small mass can be accumulated from CO photo-dissociation in a time as short as $\sim$10$^4$ yr. We develop a simple model for gas production and destruction in this system, properly accounting for CO self-shielding and shielding by neutral carbon, and introducing a removal mechanism for carbon gas. We find that the most likely scenario to explain both C$^0$ and CO observations, is one where the carbon gas is rapidly removed on a timescale of order a thousand years and the system maintains a very high CO production rate of $\sim$15 M$_\oplus$ Myr$^{-1}$, much higher than the rate of dust grind-down. We propose a possible scenario to meet these peculiar conditions: the capture of carbon onto dust grains, followed by rapid CO re-formation and re-release. In steady state, CO would continuously be recycled, producing a CO-rich gas ring that shows no appreciable spreading over time. This picture might be extended to explain other gas-rich debris disks.Comment: accepted for publication in the Ap

Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in 40–69-years subjects

[Background] Visceral fat obesity can be defined quantitatively by abdominal computed tomography, however, the usefulness of measuring visceral fat area to assess the etiology of gastrointestinal reflux disease has not been fully elucidated. [Methods] A total of 433 healthy subjects aged 40–69 years (234 men, 199 women) were included in the study. The relationship between obesity-related factors (total fat area, visceral fat area, subcutaneous fat area, waist circumference, and body mass index) and the incidence of reflux erosive esophagitis was investigated. Lifestyle factors and stomach conditions relevant to the onset of erosive esophagitis were also analyzed. [Results] The prevalence of reflux erosive esophagitis was 27.2% (118/433; 106 men, 12 women). Visceral fat area was higher in subjects with erosive esophagitis than in those without (116.6 cm2 vs. 64.9 cm2, respectively). The incidence of erosive esophagitis was higher in subjects with visceral fat obesity (visceral fat area ≥ 100 cm2) than in those without (61.2% vs. 12.8%, respectively). Visceral fat obesity had the highest odds ratio (OR) among obesity-related factors. Multivariate analysis showed that visceral fat area was associated with the incidence of erosive esophagitis (OR = 2.18), indicating that it is an independent risk factor for erosive esophagitis. In addition, daily alcohol intake (OR = 1.54), gastric atrophy open type (OR = 0.29), and never-smoking history (OR = 0.49) were also independently associated with the development of erosive esophagitis. [Conclusions] Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in subjects aged 40–69 years

Gravitational Waves in Brans-Dicke Theory : Analysis by Test Particles around a Kerr Black Hole

Analyzing test particles falling into a Kerr black hole, we study gravitational waves in Brans-Dicke theory of gravity. First we consider a test particle plunging with a constant azimuthal angle into a rotating black hole and calculate the waveform and emitted energy of both scalar and tensor modes of gravitational radiation. We find that the waveform as well as the energy of the scalar gravitational waves weakly depends on the rotation parameter of black hole $a$ and on the azimuthal angle. Secondly, using a model of a non-spherical dust shell of test particles falling into a Kerr black hole, we study when the scalar modes dominate. When a black hole is rotating, the tensor modes do not vanish even for a ``spherically symmetric" shell, instead a slightly oblate shell minimizes their energy but with non-zero finite value, which depends on Kerr parameter $a$. As a result, we find that the scalar modes dominate only for highly spherical collapse, but they never exceed the tensor modes unless the Brans-Dicke parameter \omega_{BD} \lsim 750 for $a/M=0.99$ or unless \omega_{BD} \lsim 20,000 for $a/M=0.5$, where $M$ is mass of black hole. We conclude that the scalar gravitational waves with \omega_{BD} \lsim several thousands do not dominate except for very limited situations (observation from the face-on direction of a test particle falling into a Schwarzschild black hole or highly spherical dust shell collapse into a Kerr black hole). Therefore observation of polarization is also required when we determine the theory of gravity by the observation of gravitational waves.Comment: 24 pages, revtex, 18 figures are attached with ps file

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM