Enzymatic digestion of articular cartilage results in viscoelasticity changes that are consistent with polymer dynamics mechanisms

<p>Abstract</p> <p>Background</p> <p>Cartilage degeneration via osteoarthritis affects millions of elderly people worldwide, yet the specific contributions of matrix biopolymers toward cartilage viscoelastic properties remain unknown despite 30 years of research. Polymer dynamics theory may enable such an understanding, and predicts that cartilage stress-relaxation will proceed faster when the average polymer length is shortened.</p> <p>Methods</p> <p>This study tested whether the predictions of polymer dynamics were consistent with changes in cartilage mechanics caused by enzymatic digestion of specific cartilage extracellular matrix molecules. Bovine calf cartilage explants were cultured overnight before being immersed in type IV collagenase, bacterial hyaluronidase, or control solutions. Stress-relaxation and cyclical loading tests were performed after 0, 1, and 2 days of incubation.</p> <p>Results</p> <p>Stress-relaxation proceeded faster following enzymatic digestion by collagenase and bacterial hyaluronidase after 1 day of incubation (both <it>p </it>≤ 0.01). The storage and loss moduli at frequencies of 1 Hz and above were smaller after 1 day of digestion by collagenase and bacterial hyaluronidase (all <it>p </it>≤ 0.02).</p> <p>Conclusion</p> <p>These results demonstrate that enzymatic digestion alters cartilage viscoelastic properties in a manner consistent with polymer dynamics mechanisms. Future studies may expand the use of polymer dynamics as a microstructural model for understanding the contributions of specific matrix molecules toward tissue-level viscoelastic properties.</p

Modelling the Interaction Between Racehorse Limb and Race Surface

AbstractMusculoskeletal injuries are the leading cause of racehorse fatalities and attrition. Race surface mechanics affect racehorse limb biomechanics, and therefore can affect musculoskeletal injuries. Installation of experimental race surfaces to determine their effect on racehorse limb kinematics is not financially feasible. Furthermore, field data collection is time consuming, labor intensive, and requires the use of live animals. Computational modelling provides an economical option to survey a wide range of surface mechanics and resulting effects on racehorse limb motions. This research aimed to develop and evaluate an integrated racehorse limb and race surface computational model. The interaction of a virtual galloping racehorse impacting virtual race surfaces was modelled in SIMM using combined forward/inverse dynamics. In vivo kinematic data were averaged to determine proximal forelimb, trunk, and hindlimb kinematic model profiles throughout gallop stance, as well as distal forelimb initial conditions. All distal forelimb joints and hoof translations were free to respond to external forces applied by the race surface model during stance. Race surface model coefficients were determined from previously measured race surface mechanics and forward dynamic simulations of a track-testing device. Simulation results were compared to distal forelimb motions of actual galloping racehorses on mechanically measured race surfaces. Model predicted kinematic profiles (metacarpophalangeal angle and hoof translations) had qualitative shapes and peak magnitudes within ranges of experimental data. Simulated peak metacarpophalangeal angle and hoof translations were within 11 degrees and 4cm respectively. Future model applications include estimation of the effects of variation in race surface parameters on racehorse limb biomechanics

Identification of material parameters based on Mohr-Coulomb failure criterion for bisphosphonate treated canine vertebral cancellous bone

Nanoindentation has been widely used to study bone tissue mechanical properties. The common method and equations for analyzing nanoindentation, developed by Oliver and Pharr, are based on the assumption that the material is linearly elastic. In the present study, we adjusted the constraint of linearly elastic behavior and use nonlinear finite element analysis to determine the change in cancellous bone material properties caused by bisphosphonate treatment, based on an isotropic form of the Mohr–Coulomb failure model. Thirty-three canine lumbar vertebrae were used in this study. The dogs were treated daily for 1 year with oral doses of alendronate, risedronate, or saline vehicle at doses consistent, on a mg/kg basis, to those used clinically for the treatment of post-menopausal osteoporosis. Two sets of elastic modulus and hardness values were calculated for each specimen using the Continuous Stiffness Measurement (CSM) method (ECSM and HCSM) from the loading segment and the Oliver–Pharr method (EO–P and HO–P) from the unloading segment, respectively. Young's modulus (EFE), cohesion (c), and friction angle (ϕ) were identified using a finite element model for each nanoindentation. The bone material properties were compared among groups and between methods for property identification. Bisphosphonate treatment had a significant effect on several of the material parameters. In particular, Oliver–Pharr hardness was larger for both the risedronate- and alendronate-treated groups compared to vehicle and the Mohr–Coulomb cohesion was larger for the risedronate-treated compared to vehicle. This result suggests that bisphosphonate treatment increases the hardness and shear strength of bone tissue. Shear strength was linearly predicted by modulus and hardness measured by the Oliver–Pharr method (r2 = 0.99). These results show that bisphosphonate-induced changes in Mohr–Coulomb material properties, including tissue shear cohesive strength, can be accurately calculated from Oliver–Pharr measurements of Young's modulus and hardness

RANK/RANKL/OPG pathway: genetic associations with stress fracture period prevalence in elite athletes

Context: The RANK/RANKL/OPG signalling pathway is important in the regulation of bone turnover, with single nucleotide polymorphisms (SNPs) in genes within this pathway associated with bone phenotypic adaptations. Objective: To determine whether four SNPs associated with genes in the RANK/RANKL/OPG signalling pathway were associated with stress fracture injury in elite athletes. Design, Participants, and Methods: Radiologically confirmed stress fracture history was reported in 518 elite athletes, forming the Stress Fracture Elite Athlete (SFEA) cohort. Data were analysed for the whole group, and were sub-stratified into male and cases of multiple stress fracture group. Genotypes were determined using proprietary fluorescence-based competitive allele-specific PCR assays. Results: SNPs rs3018362 (RANK) and rs1021188 (RANKL) were associated with stress fracture injury (p<0.05). 8.1% of stress fracture group and 2.8% of the non-stress fracture group were homozygote for the rare allele of rs1021188. Allele frequency, heterozygotes and homozygotes for the rare allele of rs3018362 were associated with stress fracture period prevalence (p<0.05). Analysis of the male only group showed 8.2% of rs1021188 rare allele homozygotes to have suffered a stress fracture while 2.5% of the non-stress fracture group were homozygous. In cases of multiple stress fractures, homozygotes for the rare allele of rs1021188, and individuals possessing at least one copy of the rare allele of rs4355801 (OPG) were shown to be associated with stress fracture injury (p<0.05). Conclusions: The data support an association between SNPs in the RANK/RANKL/OPG signalling pathway and the development of stress fracture injury. The association of rs3018362 (RANK) and rs1021188 (RANKL) with stress fracture injury susceptibility supports their role in the maintenance of bone health, and offers potential targets for therapeutic interventions

Galaxy Evolution Probe: a concept for a mid and far-infrared space observatory

The Galaxy Evolution Probe (GEP) is a concept for a mid and far-infrared space observatory designed to survey sky for star-forming galaxies from redshifts of z = 0 to beyond z = 4. Furthering our knowledge of galaxy formation requires uniform surveys of star-forming galaxies over a large range of redshifts and environments to accurately describe star formation, supermassive black hole growth, and interactions between these processes in galaxies. The GEP design includes a 2 m diameter SiC telescope actively cooled to 4 K and two instruments: (1) An imager to detect star-forming galaxies and measure their redshifts photometrically using emission features of polycyclic aromatic hydrocarbons. It will cover wavelengths from 10 to 400 μm, with 23 spectral resolution R = 8 filter-defined bands from 10 to 95 μm and five R = 3.5 bands from 95 to 400 μm. (2) A 24 – 193 μm, R = 200 dispersive spectrometer for redshift confirmation, identification of active galactic nuclei, and interstellar astrophysics using atomic fine-structure lines. The GEP will observe from a Sun-Earth L2 orbit, with a design lifetime of four years, devoted first to galaxy surveys with the imager and second to follow-up spectroscopy. The focal planes of the imager and the spectrometer will utilize KIDs, with the spectrometer comprised of four slit-coupled diffraction gratings feeding the KIDs. Cooling for the telescope, optics, and KID amplifiers will be provided by solar-powered cryocoolers, with a multi-stage adiabatic demagnetization refrigerator providing 100 mK cooling for the KIDs

The galaxy evolution probe

The Galaxy Evolution Probe (GEP) is a NASA Astrophysics Probe concept designed to address key questions about star formation and supermassive black hole growth in galaxies over cosmic time. GEP will achieve its goals with large mid- and far-infrared imaging and spectroscopic surveys. ..

Training drives turnover rates in racehorse proximal sesamoid bones

Focal bone lesions are often found prior to clinically relevant stress-fractures. Lesions are characterized by low bone volume fraction, low mineral density, and high levels of microdamage and are hypothesized to develop when bone tissue cannot sufficiently respond to damaging loading. It is difficult to determine how exercise drives the formation of these lesions because bone responds to mechanical loading and repairs damage. In this study, we derive steady-state rate constants for a compartment model of bone turnover using morphometric data from fractured and non-fractured racehorse proximal sesamoid bones (PSBs) and relate rate constants to racing-speed exercise data. Fractured PSBs had a subchondral focus of bone turnover and microdamage typical of lesions that develop prior to fracture. We determined steady-state model rate constants at the lesion site and an internal region without microdamage using bone volume fraction, tissue mineral density, and microdamage area fraction measurements. The derived undamaged bone resorption rate, damage formation rate, and osteoid formation rate had significant robust regression relationships to exercise intensity (rate) variables, layup (time out of exercise), and exercise 2-10&nbsp;months before death. However, the direction of these relationships varied between the damaged (lesion) and non-damaged regions, reflecting that the biological response to damaging-loading differs from the response to non-damaging loading

A Novel Method for Curvefitting the Stretched Exponential Function to Experimental Data.

The stretched exponential function has many applications in modeling numerous types of experimental relaxation data. However, problems arise when using standard algorithms to fit this function: we have observed that different initializations result in distinct fitted parameters. To avoid this problem, we developed a novel algorithm for fitting the stretched exponential model to relaxation data. This method is advantageous both because it requires only a single adjustable parameter and because it does not require initialization in the solution space. We tested this method on simulated data and experimental stress-relaxation data from bone and cartilage and found favorable results compared to a commonly-used Quasi-Newton method. For the simulated data, strong correlations were found between the simulated and fitted parameters suggesting that this method can accurately determine stretched exponential parameters. When this method was tested on experimental data, high quality fits were observed for both bone and cartilage stress-relaxation data that were significantly better than those determined with the Quasi-Newton algorithm