Cells respond to space microgravity through cytoskeleton reorganization.

Decades of spaceflight studies have provided abundant evidence that individual cells in vitro are capable of sensing space microgravity and responding with cellular changes both structurally and functionally. However, how microgravity is perceived, transmitted, and converted to biochemical signals by single cells remains unrevealed. Here in this review, over 40 cellular biology studies of real space fights were summarized. Studies on cells of the musculoskeletal system, cardiovascular system, and immune system were covered. Among all the reported cellular changes in response to space microgravity, cytoskeleton (CSK) reorganization emerges as a key indicator. Based on the evidence of CSK reorganization from space flight research, a possible mechanism from the standpoint of "cellular mechanical equilibrium" is proposed for the explanation of cellular response to space microgravity. Cytoskeletal equilibrium is broken by the gravitational change from ground to space and is followed by cellular morphological changes, cell mechanical properties changes, extracellular matrix reorganization, as well as signaling pathway activation/inactivation, all of which ultimately lead to the cell functional changes in space microgravity.

Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products.

Bone loss occurs in astronauts during long-term space flight, but the mechanisms are still unclear. We previously showed that advanced glycation end products (AGEs) were involved in microgravity-induced osteoporosis. Here, we investigated the improvement effects of blocking AGEs formation on microgravity-induced bone loss by using the AGEs formation inhibitor, irbesartan. To achieve this objective, we used a tail-suspended (TS) rat model to simulate microgravity and treated the TS rats with 50 mg/kg/day irbesartan, as well as the fluorochrome biomarkers injected into rats to label dynamic bone formation. To assess the accumulation of AGEs, pentosidine (PEN), non-enzymatic cross-links (NE-xLR), and fluorescent AGEs (fAGEs) were identified in the bone; 8-hydroxydeoxyguanosine (8-OHdG) was analyzed for the reactive oxygen species (ROS) level in the bone. Meanwhile, bone mechanical properties, bone microstructure, and dynamic bone histomorphometry were tested for bone quality assessment, and Osterix and TRAP were immunofluorescences stained for the activities of osteoblastic and osteoclastic cells. Results showed AGEs increased significantly and 8-OHdG expression in bone showed an upward trend in TS rat hindlimbs. The bone quality (bone microstructure and mechanical properties) and bone formation process (dynamic bone formation and osteoblastic cells activities) were inhibited after tail-suspension, and showed a correlation with AGEs, suggesting the elevated AGEs contributed to the disused bone loss. After being treated with irbesartan, the increased AGEs and 8-OHdG expression were significantly inhibited, suggesting irbesartan may reduce ROS to inhibit dicarbonyl compounds, thus suppressing AGEs production after tail-suspension. The inhibition of AGEs can partially alter the bone remodeling process and improve bone quality. Both AGEs accumulation and bone alterations almost occurred in trabecular bone but not in cortical bone, suggesting AGEs effects on bone remodeling under microgravity are dependent on the biological milieu.

Effects of advanced glycation end products on osteocytes mechanosensitivity.

Osteocytes are extremely sensitive to mechanical loading and govern bone remodeling process. Advanced glycation end products (AGEs) have the capacity to induce osteocyte apoptosis. In order to investigate the effects of AGEs on the mechanosensitivity of osteocytes, the osteocytic-like cells (MLO-Y4) were treated with low (50 µg/ml) and high (400 µg/ml) concentrations of AGEs for 1day and exposed to 15 dyne/cm2 of fluid shear stress. Then the F-actin cytoskeleton, prostaglandin E2(PGE2), Nitric oxide (NO), the Wnt/ß-catenin signaling pathway activity mRNA expressions were detected for osteocytes mechanical response changes; osteocalcin (OCN) and receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) were detected for the regulation on bone remodeling function of osteocytes. The results showed that AGEs accumulation inhibited the sense of osteocytes to external mechincal loading, promoted shear-induced NO and PGE2 release, suppressed the mechanosensitivity of Wnt/ß-catenin signaling pathway, and furthermore promoted OCN and RANKL/OPG mRNA expressions. These indicated AGEs had an adverse impact on the mechanosensitivity of osteocytes, and led to a negative effect on their regulation of bone remodeling process under mechanical stimulation. This work provides a new perspective to interpret the alteration mechanism of osteocytes mechanosensitivity and provides a novel clue for exploring the mechanism of osteoporosis.

The microgravity induces the ciliary shortening and an increased ratio of anterograde/retrograde intraflagellar transport of osteocytes.

It is hard to explain the decrease in mechanosensitivity of osteocytes under microgravity. Primary cilia are essential mechanosensor for osteocytes. The cilia become shorter under the simulated microgravity (SMG) environment. The cilia change may be the reason for the mechanosensitivity decrease of osteocytes under SMG. To reveal the role of primary cilia in weightless-induced osteocyte dysfunction, we investigate intraflagellar transport (IFT) to understand the mechanism of the decreased cilia length of osteocytes when subjected to SMG. We measure the number of anterograde IFT particles with GFP::IFT88 and retrograde IFT particles with OFP::IFT43 that occur at a particular transverse plane of the cilia. We also measure the expression of IFT88 and IFT43 and the size of IFT particles under SMG. Herein, the ratio of anterograde/retrograde particle number and the ratio of protein expression of IFT88/IFT43 increase under SMG. The size of anterograde IFT particles with GFP::IFT88 gets a significant decrease under SMG. Fundamentally, SMG has broken the balanced operating state of IFT and makes the IFT particles smaller. The phenomenon under SMG is intriguing.

Pharmacological Regulation of Primary Cilium Formation Affects the Mechanosensitivity of Osteocytes.

Primary cilia are responsible for sensing mechanical loading in osteocytes. However, the underlying working mechanism of cilia remains elusive. An osteocyte model is necessary to reveal the role of cilia. Furthermore, the osteocyte model should be with upregulated or downregulated primary cilium expression. Herein, we used a pharmacological method to regulate the cilium formation of osteocytes. After screening, some pharmacological agents can regulate the cilium formation of osteocytes. We performed a CCK-8 assay to analyze the optimal working conditions of the drugs for MLO-Y4 cells. The agents include chloral hydrate (CH), Gd3+, Li+, and rapamycin. The expression of cilia affects the cellular functions, including mechanosensitivity, of osteocytes. Results showed that CH downregulated the cilium formation and ciliogenesis of osteocytes. In addition, Gd3+, Li+, and rapamycin upregulated the cilium expression of osteocytes. Moreover, the cilium expression positively correlated with the mechanosensitivity of osteocytes. This work reveals the role of primary cilia in the mechanosensing of osteocytes.

The bio-response of osteocytes and its regulation on osteoblasts under vibration.

Vibration, especially at low magnitude and high frequency (LMHF), was demonstrated to be anabolic for bone, but how the LMHF vibration signal is perceived by osteocytes is not fully studied. On the other hand, the mechanotransduction of osteocytes under shear stress has been scientists' primary focus for years. Due to the small strain caused by low-magnitude vibration, whether the previous explanation for shear stress will still work for LMHF vibration is unknown. In this study, a finite element method (FEM) model based on the real geometrical shape of an osteocyte was built to compare the mechanical behaviors of osteocytes under LMHF vibration and shear stress. The bio-response of osteocytes to vibration under different frequencies, including the secretion of soluble factors and the concentration of intracellular calcium, were studied. The regulating effect of the conditioned medium (CM) from vibrated osteocytes on osteoblasts was also studied. The FEM analysis result showed the cell membrane deformation under LMHF vibration was very small (with a peak value of 1.09%) as compared to the deformation caused by shear stress (with a peak value of 6.65%). The F-actin stress fibers of osteocytes were reorganized, especially on the nucleus periphery after LMHF vibration. The vibration at 30 Hz has a promoting effect on osteocytes and the osteogenesis of osteoblasts, whereas vibration at 90 Hz was suppressive. These results lead to a conclusion that the bio-response of osteocytes to LMHF vibration is frequency-dependent and is more related to the cytoskeleton on nuclear periphery rather than the membrane deformation.

Observation of sGAG content of human hip joint cartilage in different old age groups based on EPIC micro-CT.

OBJECTIVES: To observe the age-related changes of sulfated glycosaminoglycan (sGAG) content of hip joint cartilage of elderly people based on Equilibrium Partitioning of an Ionic Contrast Agent (EPIC) micro-CT. METHODS: Seventy human hip cartilage-bone samples were collected from hip-fracture patients (ages 51-96) and divided into five groups (10 years in an age group). They were first immersed in 20% concentration of the contrast agent Meglumine Diatrizoate (MD) for 6 h at 37 °C, and then scanned by micro-CT. Following scanning, samples were stained for sGAG with toluidine blue. The X-ray attenuation and sGAG optical density were calculated by image processing. The correlation between X-ray attenuation and sGAG optical density was then analyzed. RESULTS: The X-ray mean attenuation of the cartilage increased by 18.81% from the 50-80 age groups (p < 0.01), but decreased by 7.15% in the 90 age group compared to the 80 age group. The X-ray mean attenuation of the superficial layer and middle layer increased by 31.60 % and 44.68% from the 50-80 age groups, respectively (p < 0.01), but reduced by 4.67% and 6.05% separately in the 90 age group. However, the deep layer showed no significant change with aging. The sGAG optical density showed a linear correlation (r = -0.91, p < 0.01) with the X-ray attenuation. CONCLUSION: The sGAG content of hip joint cartilage varied with aging in elderly people. The changes in superficial layer and middle layer were more evident than deep layer.

Biomechanical analysis of suture locations of the distal plantar fascia in partial foot.

PURPOSE: The aim of this study was to evaluate the rationality of the suture locations of distal plantar fascia (DPF) after foot amputation to avoid the risk factors of re-amputation or plantar fasciitis. METHODS: The tensile strain of plantar fascia (PF) in the different regions was measured by uni-axial tensile experiment. A three-dimensional (3D) finite element model was also developed to simulate tensile behaviour of PF in weight bearing conditions. The model includes 12 bones, ligaments, PF, cartilage and soft tissues. Four suture location models for the DPF were considered: the fourth and fifth DPF were sutured on the third metatarsal, the cuboid, and both the third metatarsal and the cuboid, and one un-sutured model. RESULTS: The peak tensile strain of the first, second and third PF was 0.134, 0.128 and 0.138 based on the mechanical test, respectively. The fourth and fifth DPF sutured at the cuboid and the third metatarsal could offer more favourable outcomes. The peak strain of 4.859 × 10(-2), 2.347 × 10(-2) and 1.364 × 10(-2) in the first, second and third PF showed the least outcomes in stance phase. Also, peak strain and stress of the residual PF reduced to 4.859 × 10(-2) and 1.834 MPa, respectively. The stress region was redistributed on the mid-shaft of the first and third PF and the peak stress of medial cuneiform bone evidently decreased. CONCLUSIONS: The fourth and fifth DPF suture at the third metatarsal and cuboid was appropriate for the partial foot. The findings are expected to suggest optimal surgical plan of the DPF suture and guide further therapeutic planning of partial foot patients.

Biomechanical effects of cervical arthroplasty with U-shaped disc implant on segmental range of motion and loading of surrounding soft tissue.

PURPOSE: Various design concepts have been adopted in cervical disc prostheses, including sliding articulation and standalone configuration. This study aimed to evaluate the biomechanical effects of the standalone U-shaped configuration on the cervical spine. METHODS: Based on an intact finite element model of C3-C7, a standalone U-shaped implant (DCI) was installed at C5-C6 and compared with a sliding articulation design (Prodisc-C) and an anterior fusion system. The range of motion (ROM), adjacent intradiscal pressure (IDP) and capsular ligament strain were calculated under different spinal motions. RESULTS: Compared to the intact configuration, the ROM at C5-C6 was reduced by 90% after fusion, but increased by 70% in the Prodisc-C model, while the maximum percentage change in the DCI model was 30% decrease. At the adjacent segments, up to 32% increase in ROM happened after fusion, while up to 34% decrease occurred in Prodisc-C model and 17% decrease in DCI model. The IDP increased by 11.6% after fusion, but decreased by 5.6 and 6.3% in the DCI and Prodisc-C model, respectively. The capsular ligament strain increased by 147% in Prodisc-C and by 13% in the DCI model. The DCI implant exhibited a high stress distribution. CONCLUSIONS: Spinal fusion resulted in compensatory increase of ROM at the adjacent sites, thereby elevating the IDP. Prodisc-C resulted in hyper-mobility at the operative site that led to an increase of ligament force and strain. The U-shaped implant could maintain the spinal kinematics and impose minimum influence on the adjacent soft tissues, despite the standalone configuration encountering the disadvantages of high stress distribution.

Diffusion tensor tractography of residual fibers in traumatic spinal cord injury: a pilot study.

BACKGROUND AND PURPOSE: In clinical studies, evaluating residual fiber tracts in spinal cord injuries poses serious difficulties, whereas diffusion tensor imaging (DTI) can assess alterations in fiber structural integrity. For this reason, this study aimed to determine changes in the structural integrity of residual fiber tracts via fractional anisotropy (FA) variations and fiber-tracking patterns in patients with chronic traumatic spinal cord injury (SCI). MATERIALS AND METHODS: T2-weighted and diffusion-weighted imaging was performed on four traumatic SCI patients and three healthy volunteers using a 3.0-T MR scanner. After obtaining fiber-tracking maps, FA values were measured and analyzed in residual and remote normal and healthy cords. RESULTS: Diffusion tensor tractography showed obvious destruction of fiber tracts in injured cords. In the healthy control subjects, averaged FA values ranged from 0.545 to 0.601, whereas all SCI patients had decreased FA values in both residual (0.220 ± 0.121) and remote normal fibers (0.535 ± 0.101). There were also statistically significant differences in FA values between residual and remote normal fibers in patients (P = 0.000) and between their residual and healthy control fibers (P = 0.000). No significant difference was found between remote normal and healthy cords (P = 0.312). CONCLUSION: Specific FA variations were observed in residual fibers, suggesting that DTI may be a useful tool for evaluating residual tracts in SCI patients.

Nonlinear dynamics of membrane skeleton in osteocyte.

Osteocytes play an important role in mechanosensation and conduction in bone tissue, and the change of mechanical environment can affect the sensitivity of osteocytes to external stimulation. The structure of osteocytes will be changed when they are subjected to vibrations, which influence the mechanosensitivity of osteocytes and alter the regulation of bone remodeling process. As an important mechanotransduction structure in osteocytes, the membrane skeleton greatly affects the mechanosensation and conduction of osteocytes. However, the dynamic responses of membrane skeleton to the vibration and the structural changes of membrane skeleton are unclear. Therefore, we applied a nonlinear dynamics method to explain the time-dependent changes of membrane skeleton. The semi-ellipsoidal reticulate shell structure of membrane skeleton is built based on the experimental observation in our previous work. Then, the nonlinear dynamic equations of membrane skeleton are established according to the theory of plate and shell dynamics, and the displacement-time curves, phase portraits, and Poincaré maps of membrane skeleton structure were obtained. The numeration results show that under the vibration stimulation of 15 Hz, 30 Hz, 60 Hz, and 90 Hz, the membrane skeleton is destroyed after a transient equilibrium position vibration. The vibration of 15 Hz has the most destructive effect on the membrane skeleton, the natural frequency of membrane skeleton may be less than 15 Hz. In addition, the chaos phenomenon occurs to the membrane skeleton during vibration. As a damping factor, the existence of viscosity alleviates the damage of structure. This study can help us to understand the oscillation characteristic of membrane skeleton in osteocyte.

Mechanically sensitive HSF1 is a key regulator of left-right symmetry breaking in zebrafish embryos.

The left-right symmetry breaking of vertebrate embryos requires nodal flow. However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. Here, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kupffer's vesicle of zebrafish embryos in the presence of nodal flow. Deficiency in HSF1 expression caused a significant situs inversus and disrupted gene expression asymmetry of nodal signaling proteins in zebrafish embryos. Further studies demonstrated that HSF1 is a mechanosensitive protein. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and Ca2+-Akt signaling axis are essential for the activation of HSF1 under mechanical stress in vitro and in vivo. Considering the conserved expression of HSF1 in organisms, these findings unveil a fundamental mechanism of gene expression regulation by mechanical clues during embryonic development and other physiological and pathological transformations.

Ultrasonic reflection coefficient and surface roughness index of OA articular cartilage: relation to pathological assessment.

BACKGROUND: Early diagnosis of osteoarthritis (OA) is essential for preventing further cartilage destruction and decreasing severe complications. The aims of this study are to explore the relationship between OA pathological grades and quantitative acoustic parameters and to provide more objective criteria for ultrasonic microscopic evaluation of the OA cartilage. METHODS: Articular cartilage samples were prepared from rabbit knees and scanned using ultrasound biomicroscopy (UBM). Three quantitative parameters, including the roughness index of the cartilage surface (URI), the reflection coefficients from the cartilage surface (R) and from the cartilage-bone interface (Rbone) were extracted. The osteoarthritis grades of these cartilage samples were qualitatively assessed by histology according to the grading standards of International Osteoarthritis Institute (OARSI). The relationship between these quantitative parameters and the osteoarthritis grades was explored. RESULTS: The results showed that URI increased with the OA grade. URI of the normal cartilage samples was significantly lower than the one of the OA cartilage samples. There was no significant difference in URI between the grade 1 cartilage samples and the grade 2 cartilage samples. The reflection coefficient of the cartilage surface reduced significantly with the development of OA (p < 0.05), while the reflection coefficient of the cartilage-bone interface increased with the increase of grade. CONCLUSION: High frequency ultrasound measurements can reflect the changes in the surface roughness index and the ultrasound reflection coefficients of the cartilage samples with different OA grades. This study may provide useful information for the quantitative ultrasonic diagnosis of early OA.

The effect of physical loading on calcaneus quantitative ultrasound measurement: a cross-section study.

BACKGROUND: Physical loading leads to a deformation of bone microstructure and may influence quantitative ultrasound (QUS) parameters. This study aims at evaluating the effect of physical loading on bone QUS measurement, and further, on the potential of diagnosing osteoporosis using QUS method under physical loading condition. METHODS: 16 healthy young females (control group) and 45 postmenopausal women (divided into 3 groups according to the years since menopause (YSM)) were studied. QUS parameters were measured at calcaneus under self-weight loading (standing) and no loading (sitting) conditions. Weight-normalized QUS parameter (QUS parameter measured under loading condition divided by the weight of the subject) was proposed to evaluate the influence of loading. T-test, One-Way analysis of variance (one way ANOVA) and receiver operating characteristic (ROC) analysis were applied for analysis. RESULTS: In QUS parameters, mainly normalized broadband ultrasound attenuation (nBUA), measured with loading significantly differed from those measured without loading (p < 0.05). The relative changes of weight-normalized QUS parameters on postmenopausal women with respect to premenopausal women under loading condition were larger than those on traditional QUS parameters measured without loading. In ROC analysis, weight-normalized QUS parameters showed their stronger discriminatory ability for menopause. CONCLUSIONS: Physical loading substantially influenced bone QUS measurement (mainly nBUA). Weight-normalized QUS parameters can discriminate menopause more effectively. By considering the high relationship between menopause and osteoporosis, an inference was drawn that adding physical loading during measurement may be a probable way to improve the QUS based osteoporosis diagnosis.

Comparative study on measured variables and sensitivity to bone microstructural changes induced by weightlessness between in vivo and ex vivo micro-CT scans.

Depending on the experimental design, micro-CT can be used to examine bones either in vivo or ex vivo (excised fresh or formalin-fixed). In this study we investigated if differences exist in the variables measured by micro-CT between in vivo and ex vivo scans and which kind of scan is more sensitive to the changes of bone microstructure induced by simulated weightlessness. Rat tail suspension was used to simulate the weightless condition. The same bone from either normal or tail-suspended rats was scanned by micro-CT both in vivo and ex vivo (fresh and fixed by formalin). Then, bone mineral density (BMD) and microstructural characteristics were analyzed. The results showed that no significant differences existed in the microstructural parameters of trabecular bone among in vivo, fresh, and formalin-fixed bone scans from both femurs and tibias, although BMD exhibited differences. On the other hand, most parameters of the tail-suspended rats measured by micro-CT deteriorated compared with controls. Ex vivo scanning appeared to be more sensitive to bone microstructural changes induced by tail suspension than in vivo scanning. In general, the results indicate that values obtained in vivo and ex vivo (fresh and fixed) are comparable, thus allowing for meaningful comparison of experimental results from different studies irrespective of the type of scans. In addition, this study suggests that it is better to use ex vivo scanning when evaluating bone microstructure under weightlessness. However, researchers can select any type of scan depending upon the objective and the demands of the experiment.

[The Biomechanics Influence of unilateral laminectomy and discectomy surgery on the adjacent different grades of Disc Degeneration].

OBJECTIVES: To study the stress distribution of the adjacent different grades of disc degeneration underwenting unilateral laminectomy and discectomy surgery using non-linear finite element analysis. METHODS: Based on the lumbar CT scans, the finite element model (FEM) of lumbar spinal segment (L3-L5) was established. According to L3-L4 intervertebral disc degeneration, different grades of disc degeneration (healthy, mild, moderate and severe) models were established and unilateral laminectomy and discectomy surgery were also established. Physiological action such as flexion, extension, lateral bending and lateral rotation was simulated and the von Mises stress in the nucleus pulposus and annulus fibrosus matrix of L3-L4 disc was investigated. RESULTS: After unilateral laminectomy and discectomy surgery, the extremum value of von Mises stress of nucleus pulposus and annulus fibrosus matrix was maximum during extension and minimus left bending in the healthy intervertebral disc. Compared with healthy disc, the increment of extremum value was found during left bending in the mildly degenerated disc. When the value decreased in the moderately degenerated disc, but still higher than that in the healthy disc. When the adjacent disc is severely degenerated, the extremum value of nucleus pulposus decreased, in addition to axial rotation, and even lower than that of healthy disc. The value of annulus matrix decreased and still higher than that of healthy disc, especially during left bending. CONCLUSIONS: After unilateral laminectomy and discectomy surgery, avoiding lateral bending will reduce the abnormal stress in the degenerated disc and decreased the risk of accelerating disc degeneration.

Non-amputated limb muscle coordination of unilateral transfemoral amputees.

Unilateral transfemoral amputees rely heavily on non-amputated limb muscles to regulate the prosthetic gait. In this study, we compared the non-amputated limb muscle coordination of eight unilateral transfemoral amputees to eight able-bodied controls. Inverse dynamics approach was conducted via a musculoskeletal model to obtain lower limb joint moments and muscle forces. In addition to the muscle forces at the instants of peak joint moments and the maximum muscle forces, the peak joint moments of the lower limbs were also investigated. The results showed that there were significant differences of muscle forces between the non-amputated limbs and the controls at the instant of peak hip extension moment, although the peak hip extension moments themselves were not significantly different between the two groups. The non-amputated limbs had significantly smaller peak hip flexion moment and peak knee extension moment, with significant differences between the muscle forces of non-amputated limbs and controls at the two instants. There was no significant difference between the muscle forces of the non-amputated limbs and controls at the peak knee flexion moment instant, despite the fact that the non-amputated limbs had significantly higher peak knee flexion moments. In addition, the non-amputated limbs had significantly smaller maximum muscle forces than the controls. These results demonstrate that amputees modify their muscle coordination to adapt to the specific joint requirements of the prosthetic gait. Our findings suggest the possibility of non-amputated limb muscle atrophy due to the decrease in the peak muscle forces during walking.

Extracellular Matrix Stiffness Regulates DNA Methylation by PKCα-Dependent Nuclear Transport of DNMT3L.

Extracellular matrix (ECM) stiffness has profound effects on the regulation of cell functions. DNA methylation is an important epigenetic modification governing gene expression. However, the effects of ECM stiffness on DNA methylation remain elusive. Here, it is reported that DNA methylation is sensitive to ECM stiffness, with a global hypermethylation under stiff ECM condition in mouse embryonic stem cells (mESCs) and embryonic fibroblasts compared with soft ECM. Stiff ECM enhances DNA methylation of both promoters and gene bodies, especially the 5' promoter regions of pluripotent genes. The enhanced DNA methylation is functionally required for the loss of pluripotent gene expression in mESCs grown on stiff ECM. Further experiments reveal that the nuclear transport of DNA methyltransferase 3-like (DNMT3L) is promoted by stiff ECM in a protein kinase C α (PKCα)-dependent manner and DNMT3L can be binding to Nanog promoter regions during cell-ECM interactions. These findings unveil DNA methylation as a novel target for the mechanical sensing mechanism of ECM stiffness, which provides a conserved mechanism for gene expression regulation during cell-ECM interactions.

Body-weight distribution on forelimbs in rat tail-suspension model.

To understand the tail-suspension model to simulate weightlessness better, this study was to investigate the relationship of the amount of body weight supported by forelimbs between the tilt angles of rat in the model. Normal rat had at least two basic postures. One was standing or walking, in which the forelimbs bear 44.6% of the body weight; the other one was resting, in which 23.9% of body weight was placed on the forelimbs. As for tail-suspended rat, body-weight distribution on forelimbs was linearly related to tilt angle. The linear relationship was y = -0.7423x + 70.849, R2 = 0.9269. The tilt angle should be approximately 35 degrees if normal standing load of 44.6% body weight was placed on the forelimbs. On the other hand, it should be approximately 63 degrees if normal resting load of 23.9% of body weight was placed on forelimbs. Furthermore, the body load on forelimbs in tail-suspension model became much larger if the period of different postures was considered. Therefore, it should be careful if forelimbs are used to be as convenient internal control in tail-suspended rats.

The Biomechanical Relationship between Hallux Valgus Deformity and Metatarsal Pain.

Metatarsal pain is a common pathological outcome in patients with a hallux valgus (HV) deformity. However, the relationship between the degree of HV deformity and metatarsal pain has not been systematically examined. The purpose of the present study was to investigate the correlation between metatarsal pain and the degree of HV deformity. Between October 2017 and September 2018, 512 HV patients (944 feet) participated in an evaluation of their HV angle (HVA) using X-ray images. The participants were divided into four groups corresponding to their HVA (<15°, 15° to 20°, 21° to 40°, or >40°). Load rate, impulse, contact duration, and contact area were measured and recorded as dynamic gait parameters using the RsScan system. Data were evaluated using SPSS statistical software. The visual analog scale (VAS) was used to assess metatarsal pain. For the four HV deformity groups, the peak value of impulse and contact duration was concentrated on the second and third metatarsals (Meta2 and Meta3) (P < 0.05); contact area was also shown on metatarsals 1, 2, and 5 (P < 0.05). Metatarsal pain on Meta2 had the highest VAS score (VAS: 6.57), followed by Meta3 (Mean VAS: 5.72). In the HV > 40° group, the load location on Meta2 was transferred to Meta1. The percent of pain attributed to Meta2 and Meta3 was also increased in this group. These findings illustrated that metatarsal pain was primarily located on Meta2 and Meta3 in the different degrees of HV deformity. This information can provide the location to target for pain relief and help guide further rehabilitation.