Dysregulation of the corticotropin‐releasing factor (
The role and regulation of
These results reveal that repeated cycles of binge drinking alter
To elucidate the role of decorin, a small leucine‐rich proteoglycan, in the degradation of cartilage matrix during the progression of post‐traumatic osteoarthritis (
Three‐month–old decorin‐null (Dcn−/−) and inducible decorin‐knockout (Dcni
In both Dcn−/−and Dcni
In post‐traumatic
- Award ID(s):
- 1662544
- NSF-PAR ID:
- 10456511
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Arthritis & Rheumatology
- Volume:
- 72
- Issue:
- 8
- ISSN:
- 2326-5191
- Page Range / eLocation ID:
- p. 1266-1277
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Background CRF ) system has been observed in rodent models of binge drinking, with a large focus onCRF receptor 1 (CRF ‐R1). The role ofCRF ‐binding protein (CRF ‐BP ), a key regulator ofCRF activity, in binge drinking is less well understood. In humans, single‐nucleotide polymorphisms inCRHBP CRF ‐BP in vulnerability to alcohol addiction.Methods CRF ‐BP in binge drinking were examined in mice exposed to the drinking in the dark (DID ) paradigm. Using in situ hybridization, the regulation ofCRF ‐BP ,CRF ‐R1, andCRF mRNA expression was determined in the stress and reward systems of C57BL /6J mice after repeated cycles ofDID . To determine the functional role ofCRF ‐BP in binge drinking,CRF ‐BP knockout (CRF ‐BP KO ) mice were exposed to 6 cycles ofDID , during which alcohol consumption was measured and compared to wild‐type mice.Results CRF ‐BP mRNA expression was significantly decreased in the prelimbic (PL ) and infralimbic medial prefrontal cortex (mPFC ) of C57BL /6J mice after 3 cycles and in thePL mPFC after 6 cycles ofDID . No significant changes inCRF orCRF ‐R1 mRNA levels were observed in mPFC , ventral tegmental area, bed nucleus of the stria terminalis, or amygdala after 3 cycles ofDID .CRF ‐BP KO mice do not show significant alterations in drinking compared to wild‐type mice across 6 cycles of DID.Conclusions CRF ‐BP mRNA expression in the mPFC , a region responsible for executive function and regulation of emotion and behavior, including responses to stress. We observed a persistent decrease inCRF ‐BP mRNA expression in the mPFC after 3 and 6DID cycles, which may allow for increasedCRF signaling atCRF ‐R1 and contribute to excessive binge‐like ethanol consumption. -
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Background Healthy articular cartilage presents structural gradients defined by distinct zonal patterns through the thickness, which may be disrupted in the pathogenesis of several disorders. Analysis of textural patterns using quantitative MRI data may identify structural gradients of healthy or degenerating tissue that correlate with early osteoarthritis (OA).
Purpose To quantify spatial gradients and patterns in MRI data, and to probe new candidate biomarkers for early severity of OA.
Study Type Retrospective study.
Subjects Fourteen volunteers receiving total knee replacement surgery (eight males/two females/four unknown, average age ± standard deviation: 68.1 ± 9.6 years) and 10 patients from the OA Initiative (OAI) with radiographic OA onset (two males/eight females, average age ± standard deviation: 57.7 ± 9.4 years; initial Kellgren‐Lawrence [KL] grade: 0; final KL grade: 3 over the 10‐year study).
Field Strength/Sequence 3.0‐T and 14.1‐T, biomechanics‐based displacement‐encoded imaging, fast spin echo, multi‐slice multi‐echo
T2 mapping.Assessment We studied structure and strain in cartilage explants from volunteers receiving total knee replacement, or structure in cartilage of OAI patients with progressive OA. We calculated spatial gradients of quantitative MRI measures (eg, T2) normal to the cartilage surface to enhance zonal variations. We compared gradient values against histologically OA severity, conventional relaxometry, and/or KL grades.
Statistical Tests Multiparametric linear regression for evaluation of the relationship between residuals of the mixed effects models and histologically determined OA severity scoring, with a significance threshold at
α = 0.05.Results Gradients of individual relaxometry and biomechanics measures significantly correlated with OA severity, outperforming conventional relaxometry and strain metrics. In human explants, analysis of spatial gradients provided the strongest relationship to OA severity (
R 2 = 0.627). Spatial gradients of T2 from OAI data identified variations in radiographic (KL Grade 2) OA severity in single subjects, while conventional T2 alone did not.Data Conclusion Spatial gradients of quantitative MRI data may improve the predictive power of noninvasive imaging for early‐stage degeneration.
Evidence Level 1
Technical Efficacy Stage 1
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Structured Abstract Objectives To investigate the ploughing mechanism associated with tractional force formation on the temporomandibular joint (
TMJ ) disc surface.Setting and Sample Population Ten left
TMJ discs were harvested from 6‐ to 8‐month‐old male Yorkshire pigs.Materials and Methods Confined compression tests characterized mechanical
TMJ disc properties, which were incorporated into a biphasic finite element model (FEM ). TheFEM was established to investigate load carriage within the extracellular matrix (ECM ) and the ploughing mechanism during tractional force formation by simulating previous in vitro plough experiments.Results Biphasic mechanical properties were determined in five
TMJ disc regions (average±standard deviation for aggregate modulus: 0.077±0.040MP a; hydraulic permeability: 0.88±0.37×10−3mm4/Ns).FE simulation results demonstrated that interstitial fluid pressurization is a dominant loading support mechanism in theTMJ disc. Increased contact load and duration led to increased solidECM strain and stress within, and increased ploughing force on the surface of the disc.Conclusion Sustained mechanical loading may play a role in load carriage within the
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Abstract Nitritation‐anammox treatment can be a potentially energy‐ and resource‐efficient technology for treating mainstream wastewater. However, the issue of nitrate residue from anammox treatment remains to be addressed. Herein, external recirculation of the anammox effluent to a hybrid anaerobic reactor (
HAR ), which was also to provide a continuous flow with lowCOD /N for the nitritation‐anammox reactor, was employed to decrease the residue compounds. The recirculation ratio of 50% was observed to be the optimal to achieve the best overall performance with potential savings in energy demand. Specifically, in the operation scenario ofR = 50%, the highestCOD removal of ~90% by theHAR was achieved. Meanwhile, the lowestCOD /NH 4+‐N ratio of ~2.0 in theHAR effluent ensured the lowest observedNO 3−‐N/NH 4+‐N ratio of ~14% in the nitritation‐anammox reactor. These results have demonstrated the feasibility of applying external recirculation for nitrate residue removalvia denitrification in the anaerobic pretreatment stage.Practitioner points Nitritation‐anammox treatment is an attractive method for mainstream wastewater treatment.
Nitrate residue from anammox processes contributes to total nitrogen in the final effluent.
Recirculation of anammox effluent to an anaerobic reactor can decrease nitrate residue.
A recirculation ratio of 50% results in a low COD/NH4+ratio of 2 that benefits the subsequent anammox.
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Objective Transforming growth factor β (TGFβ) signaling plays a complex tissue‐specific and nonlinear role in osteoarthritis (OA). This study was conducted to determine the osteocytic contributions of TGFβ signaling to OA.
Methods To identify the role of osteocytic TGFβ signaling in joint homeostasis, we used 16‐week‐old male mice (n = 9–11 per group) and female mice (n = 7–11 per group) with an osteocyte‐intrinsic ablation of TGFβ receptor type II (TβRIIocy−/−mice) and assessed defects in cartilage degeneration, subchondral bone plate (SBP) thickness, and SBP sclerostin expression. To further investigate these mechanisms in 16‐week‐old male mice, we perturbed joint homeostasis by subjecting 8‐week‐old mice to medial meniscal/ligamentous injury (MLI), which preferentially disrupts the mechanical environment of the medial joint to induce OA.
Results In all contexts, independent of sex, genotype, or medial or lateral joint compartment, increased SBP thickness and SBP sclerostin expression were spatially associated with cartilage degeneration. Male TβRIIocy−/−mice, but not female TβRIIocy−/−mice, had increased cartilage degeneration, increased SBP thickness, and higher levels of SBP sclerostin compared with control mice (all
P < 0.05), demonstrating that the role of osteocytic TGFβ signaling on joint homeostasis is sexually dimorphic. With changes in joint mechanics following injury, control mice had increased SBP thickness, subchondral bone volume, and SBP sclerostin expression (allP < 0.05). TβRIIocy−/−mice, however, were insensitive to subchondral bone changes with injury, suggesting that mechanosensation at the SBP requires osteocytic TGFβ signaling.Conclusion Our results provide new evidence that osteocytic TGFβ signaling is required for a mechanosensitive response to injury, and that osteocytes control SBP homeostasis to maintain cartilage health, identifying osteocytic TGFβ signaling as a novel therapeutic target for OA.
