Matrix modification for enhancing the transport properties of the human cartilage endplate to improve disc nutrition.

Poor solute transport through the cartilage endplate (CEP) impairs disc nutrition and could be a key factor that limits the success of intradiscal biologic therapies. Here we demonstrate that treating the CEP with matrix metalloproteinase-8 (MMP-8) reduces the matrix constituents that impede solute uptake and thereby improves nutrient diffusion. Human CEP tissues harvested from four fresh cadaveric lumbar spines (age range: 38-66 years old) were treated with MMP-8. Treatment caused a dose-dependent reduction in sGAG, localized reductions to the amount of collagen, and alterations to collagen structure. These matrix modifications corresponded with 16-24% increases in the uptake of a small solute (376 Da). Interestingly, the effects of MMP-8 treatment depended on the extent of non-enzymatic glycation: treated CEPs with high concentrations of advanced glycation end products (AGEs) exhibited the lowest uptake compared to treated CEPs with low concentrations of AGEs. Moreover, AGE concentrations were donor-specific, and the donor tissues with the highest AGE concentrations appeared to have lower uptake than would be expected based on the initial amounts of collagen and sGAG. Finally, increasing solute uptake in the CEP improved cell viability inside diffusion chambers, which supports the nutritional relevance of enhancing the transport properties of the CEP. Taken together, our results provide new insights and in vitro proof-of-concept for a treatment approach that could improve disc nutrition for biologic therapy: specifically, matrix reduction by MMP-8 can enhance solute uptake and nutrient diffusion through the CEP, and AGE concentration appears to be an important, patient-specific factor that influences the efficacy of this approach

ISSLS PRIZE IN BIOENGINEERING SCIENCE 2019: biomechanical changes in dynamic sagittal balance and lower limb compensatory strategies following realignment surgery in adult spinal deformity patients.

Study designA longitudinal cohort study.ObjectiveTo define a set of objective biomechanical metrics that are representative of adult spinal deformity (ASD) post-surgical outcomes and that may forecast post-surgical mechanical complications. Current outcomes for ASD surgical planning and post-surgical assessment are limited to static radiographic alignment and patient-reported questionnaires. Little is known about the compensatory biomechanical strategies for stabilizing sagittal balance during functional movements in ASD patients.MethodsWe collected in-clinic motion data from 15 ASD patients and 10 controls during an unassisted sit-to-stand (STS) functional maneuver. Joint motions were measured using noninvasive 3D depth mapping sensor technology. Mathematical methods were used to attain high-fidelity joint-position tracking for biomechanical modeling. This approach provided reliable measurements for biomechanical behaviors at the spine, hip, and knee. These included peak sagittal vertical axis (SVA) over the course of the STS, as well as forces and muscular moments at various joints. We compared changes in dynamic sagittal balance (DSB) metrics between pre- and post-surgery and then separately compared pre- and post-surgical data to controls.ResultsStandard radiographic and patient-reported outcomes significantly improved following realignment surgery. From the DSB biomechanical metrics, peak SVA and biomechanical loads and muscular forces on the lower lumbar spine significantly reduced following surgery (- 19 to - 30%, all p < 0.05). In addition, as SVA improved, hip moments decreased (- 28 to - 65%, all p < 0.05) and knee moments increased (+ 7 to + 28%, p < 0.05), indicating changes in lower limb compensatory strategies. After surgery, DSB data approached values from the controls, with some post-surgical metrics becoming statistically equivalent to controls.ConclusionsLongitudinal changes in DSB following successful multi-level spinal realignment indicate reduced forces on the lower lumbar spine along with altered lower limb dynamics matching that of controls. Inadequate improvement in DSB may indicate increased risk of post-surgical mechanical failure. These slides can be retrieved under Electronic Supplementary Material

Chondrogenic Differentiation of Human Mesenchymal Stem Cells in Three-Dimensional Alginate Gels

We characterized the temporal changes in chondrogenic genes and developed a staging scheme for in vitro chondrogenic differentiation of human mesenchymal stem cells (hMSCs) in three-dimensional (3D) alginate gels. A time-dependent accumulation of glycosaminoglycans, aggrecan, and type II collagen was observed in chondrogenic but not in basal constructs over 24 days. qRT-PCR demonstrated a largely characteristic temporal pattern of chondrogenic markers and provided a basis for staging the cellular phenotype into four stages. Stage I (days 0–6) was defined by collagen types I and VI, Sox 4, and BMP-2 showing peak expression levels. In stage II (days 6–12), gene expression for cartilage oligomeric matrix protein, HAPLN1, collagen type XI, and Sox 9 reached peak levels, while gene expression of matrilin 3, Ihh, Homeobox 7, chondroadherin, and WNT 11 peaked at stage III (days 12–18). Finally, cells in stage IV (days 18–24) attained peak levels of aggrecan; collagen IX, II, and X; osteocalcin; fibromodulin; PTHrP; and alkaline phosphatase. Gene profiles at stages III and IV were analogous to those in juvenile articular and adult nucleus pulposus chondrocytes. Gene ontology analyses also demonstrated a specific expression pattern of several putative novel marker genes. These data provide comprehensive insights on chondrogenesis of hMSCs in 3D gels. The derivation of this staging scheme may aid in defining maximally responsive time points for mechanobiological modulation of constructs to produce optimally engineered tissues.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63385/1/tea.2007.0272.pd

Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis.

Osteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function. Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in the medial compartment of OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. As a step toward evaluating the causality of PLR suppression in OA, we ablated the PLR enzyme MMP13 in osteocytes while leaving chondrocytic MMP13 intact, using Cre recombinase driven by the 9.6-kb DMP1 promoter. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content, change chondrocyte production of collagen II, aggrecan, and MMP13, and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, defects in PLR coincide with cartilage defects. Osteocyte-derived MMP13 emerges as a critical regulator of cartilage homeostasis, likely via its effects on PLR. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and suggest a causal role for suppressed perilacunar/canalicular remodeling in osteoarthritis

The DEEP3 Galaxy Redshift Survey: The Impact of Environment on the Size Evolution of Massive Early-type Galaxies at Intermediate Redshift

Using data drawn from the DEEP2 and DEEP3 Galaxy Redshift Surveys, we investigate the relationship between the environment and the structure of galaxies residing on the red sequence at intermediate redshift. Within the massive (10 < log(M*/Msun) < 11) early-type population at 0.4 < z <1.2, we find a significant correlation between local galaxy overdensity (or environment) and galaxy size, such that early-type systems in higher-density regions tend to have larger effective radii (by ~0.5 kpc or 25% larger) than their counterparts of equal stellar mass and Sersic index in lower-density environments. This observed size-density relation is consistent with a model of galaxy formation in which the evolution of early-type systems at z < 2 is accelerated in high-density environments such as groups and clusters and in which dry, minor mergers (versus mechanisms such as quasar feedback) play a central role in the structural evolution of the massive, early-type galaxy population.Comment: 11 pages, 5 figures, 2 tables; resubmitted to MNRAS after addressing referee's comments (originally submitted to journal on August 16, 2011

Detection of postoperative granulation tissue with an ICG-enhanced integrated OI-/X-ray System

<p>Abstract</p> <p>Background</p> <p>The development of postoperative granulation tissue is one of the main postoperative risks after lumbar spine surgery. This granulation tissue may lead to persistent or new clinical symptoms or complicate a follow up surgery. A sensitive non-invasive imaging technique, that could diagnose this granulation tissue at the bedside, would help to develop appropriate treatments. Thus, the purpose of this study was to establish a fast and economic imaging tool for the diagnosis of granulation tissue after lumbar spine surgery, using a new integrated Optical Imaging (OI)/X-ray imaging system and the FDA-approved fluorescent contrast agent Indocyanine Green (ICG).</p> <p>Methods</p> <p>12 male Sprague Dawley rats underwent intervertebral disk surgery. Imaging of the operated lumbar spine was done with the integrated OI/X-ray system at 7 and 14 days after surgery. 6 rats served as non-operated controls. OI/X-ray scans of all rats were acquired before and after intravenous injection of the FDA-approved fluorescent dye Indocyanine Green (ICG) at a dose of 1 mg/kg or 10 mg/kg. The fluorescence signal of the paravertebral soft tissues was compared between different groups of rats using Wilcoxon-tests. Lumbar spines and paravertebral soft tissues were further processed with histopathology.</p> <p>Results</p> <p>In both dose groups, ICG provided a significant enhancement of soft tissue in the area of surgery, which corresponded with granulation tissue on histopathology. The peak and time interval of fluorescence enhancement was significantly higher using 10 mg/kg dose of ICG compared to the 1 mg/kg ICG dose. The levels of significance were p < 0.05. Fusion of OI data with X-rays allowed an accurate anatomical localization of the enhancing granulation tissue.</p> <p>Conclusion</p> <p>ICG-enhanced OI is a suitable technique to diagnose granulation tissue after lumbar spine surgery. This new imaging technique may be clinically applicable for postoperative treatment monitoring. It could be also used to evaluate the effect of anti-inflammatory drugs and may even allow evaluations at the bedside with new hand-held OI scanners.</p

The Advanced Camera for Surveys General Catalog: Structural Parameters for Approximately Half A Million Galaxies

We present the Advanced Camera for Surveys General Catalog (ACS-GC), a photometric and morphological database using publicly available data obtained with the Advanced Camera for Surveys (ACS) instrument on the Hubble Space Telescope. The goal of the ACS-GC database is to provide a large statistical sample of galaxies with reliable structural and distance measurements to probe the evolution of galaxies over a wide range of look-back times. The ACS-GC includes approximately 470,000 astronomical sources (stars + galaxies) derived from the AEGIS, COSMOS, GEMS, and GOODS surveys. Galapagos was used to construct photometric (SEXTRACTOR) and morphological (GALFIT) catalogs. The analysis assumes a single Sersic model for each object to derive quantitative structural parameters. We include publicly available redshifts from the DEEP2, COMBO-17, TKRS, PEARS, ACES, CFHTLS, and zCOSMOS surveys to supply redshifts (spectroscopic and photometric) for a considerable fraction (similar to 74%) of the imaging sample. The ACS-GC includes color postage stamps, GALFIT residual images, and photometry, structural parameters, and redshifts combined into a single catalog.NASA/ESA GO-10134, GO-09822, GO-09425.01, GO-09583.01, GO-9500NASA NAS 5-26555NSF AST00-71048NASA LTSA NNG04GC89GESO Paranal Observatory LP175.A-0839Astronom

The Persistence of Cool Galactic Winds in High Stellar Mass Galaxies Between z~1.4 and ~1

We present an analysis of the MgII 2796, 2803 and FeII 2586, 2600 absorption line profiles in coadded spectra of 468 galaxies at 0.7 < z < 1.5. The galaxy sample, drawn from the Team Keck Treasury Redshift Survey of the GOODS-N field, has a range in stellar mass (M_*) comparable to that of the sample at z~1.4 analyzed in a similar manner by Weiner et al. (2009; W09), but extends to lower redshifts and has specific star formation rates which are lower by ~0.6 dex. We identify outflows of cool gas from the Doppler shift of the MgII absorption lines and find that the equivalent width (EW) of absorption due to outflowing gas increases on average with M_* and star formation rate (SFR). We attribute the large EWs measured in spectra of the more massive, higher-SFR galaxies to optically thick absorbing clouds having large velocity widths. The outflows have hydrogen column densities N(H) > 10^19.3 cm^-2, and extend to velocities of ~500 km/s. While galaxies with SFR > 10 Msun/yr host strong outflows in both this and the W09 sample, we do not detect outflows in lower-SFR (i.e., log M_*/Msun < 10.5) galaxies at lower redshifts. Using a simple galaxy evolution model which assumes exponentially declining SFRs, we infer that strong outflows persist in galaxies with log M_*/Msun > 10.5 as they age between z=1.4 and z~1, presumably because of their high absolute SFRs. Finally, using high resolution HST/ACS imaging in tandem with our spectral analysis, we find evidence for a weak trend (at 1 sigma significance) of increasing outflow absorption strength with increasing galaxy SFR surface density.Comment: Submitted to ApJ. 25 pages, 19 figures, Figure 2 reduced in resolution. Uses emulateapj forma

Smooth(er) Stellar Mass Maps in CANDELS: Constraints on the Longevity of Clumps in High-redshift Star-forming Galaxies

We perform a detailed analysis of the resolved colors and stellar populations of a complete sample of 323 star-forming galaxies at 0.5 < z < 1.5, and 326 star-forming galaxies at 1.5 < z < 2.5 in the ERS and CANDELS-Deep region of GOODS-South. Galaxies were selected to be more massive than 10^10 Msun and have specific star formation rates above 1/t_H. We model the 7-band optical ACS + near-IR WFC3 spectral energy distributions of individual bins of pixels, accounting simultaneously for the galaxy-integrated photometric constraints available over a longer wavelength range. We analyze variations in rest-frame color, stellar surface mass density, age, and extinction as a function of galactocentric radius and local surface brightness/density, and measure structural parameters on luminosity and stellar mass maps. We find evidence for redder colors, older stellar ages, and increased dust extinction in the nuclei of galaxies. Big star-forming clumps seen in star formation tracers are less prominent or even invisible on the inferred stellar mass distributions. Off-center clumps contribute up to ~20% to the integrated SFR, but only 7% or less to the integrated mass of all massive star-forming galaxies at z ~ 1 and z ~ 2, with the fractional contributions being a decreasing function of wavelength used to select the clumps. The stellar mass profiles tend to have smaller sizes and M20 coefficients, and higher concentration and Gini coefficients than the light distribution. Our results are consistent with an inside-out disk growth scenario with brief (100 - 200 Myr) episodic local enhancements in star formation superposed on the underlying disk. Alternatively, the young ages of off-center clumps may signal inward clump migration, provided this happens efficiently on the order of an orbital timescale.Comment: Accepted by The Astrophysical Journal, 27 pages, 1 table, 16 figure