[The effect of Ba Duan Jin on the balance of community-dwelling older adults: a cluster randomized control trial].

Objective: To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults. Methods: A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test. Results: A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95%CI: 2.23-3.88) points (P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95%CI: 4.03-5.37) points (P<0.001). Ba Duan Jin showed significant improvement (P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions: This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Immature bovine cartilage wear is due to fatigue failure from repetitive compressive forces and not reciprocating frictional forces.

OBJECTIVE: Wear of articular cartilage is not well understood. We hypothesize that cartilage wears due to fatigue failure in repetitive compression instead of reciprocating friction. DESIGN: This study compares reciprocating sliding of immature bovine articular cartilage against glass in two testing configurations: (1) a stationary contact area configuration (SCA), which results in static compression, interstitial fluid depressurization, and increasing friction coefficient during reciprocating sliding, and (2) a migrating contact area configuration (MCA), which maintains pressurization and low friction while producing repetitive compressive loading in addition to reciprocating sliding. Contact pressure, sliding duration, and sliding distance were controlled to be similar between test groups. RESULTS: SCA tests exhibited an average friction coefficient of µ=0.084±0.032, while MCA tests exhibited a lower average friction coefficient of µ=0.020±0.008 (p<10-4). Despite the lower friction, MCA cartilage samples exhibited clear surface damage with a significantly greater average surface deviation from a fitted plane after wear testing (Rq=0.125±0.095 mm) than cartilage samples slid in a SCA configuration (Rq=0.044±0.017 mm, p=0.002), which showed minimal signs of wear. Polarized light microscopy confirmed that delamination damage occurred between the superficial and middle zones of the articular cartilage in MCA samples. CONCLUSIONS: The greatest wear was observed in the group with lowest friction coefficient, subjected to cyclical instead of static compression, implying that friction is not the primary driver of cartilage wear. Delamination between superficial and middle zones implies the main mode of wear is fatigue failure under cyclical compression, not fatigue or abrasion due to reciprocating frictional sliding.

Comprehensive Associations between Acidosis and the Skeleton in Patients with Kidney Disease.

SIGNIFICANCE STATEMENT: Renal osteodystrophy (ROD) contributes substantially to morbidity in CKD, including increased fracture risk. Metabolic acidosis (MA) contributes to the development of ROD, but an up-to-date skeletal phenotype in CKD-associated acidosis has not been described. We comprehensively studied associations between acidosis and bone in patients with CKD using advanced methods to image the skeleton and analyze bone-tissue, along with biochemical testing. Cross-sectionally, acidosis was associated with higher markers of bone remodeling and female-specific impairments in cortical and trabecular bone quality. Prospectively, acidosis was associated with cortical expansion and trabecular microarchitectural deterioration. At the bone-tissue level, acidosis was associated with deficits in bone mineral content. Future work investigating acidosis correction on bone quality is warranted. BACKGROUND: Renal osteodystrophy is a state of impaired bone quality and strength. Metabolic acidosis (MA) is associated with alterations in bone quality including remodeling, microarchitecture, and mineralization. No studies in patients with CKD have provided a comprehensive multimodal skeletal phenotype of MA. We aim to describe the structure and makeup of bone in patients with MA in the setting of CKD using biochemistry, noninvasive imaging, and histomorphometry. METHODS: The retrospective cross-sectional analyses included 180 patients with CKD. MA was defined as bicarbonate ≤22 mEq/L. We evaluated circulating bone turnover markers and skeletal imaging with dual energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subset of 54 participants had follow-up. We assessed associations between baseline and change in bicarbonate with change in bone outcomes. Histomorphometry, microCT, and quantitative backscatter electron microscopy assessed bone biopsy outcomes in 22 participants. RESULTS: The mean age was 68±10 years, 54% of participants were male, and 55% were White. At baseline, acidotic subjects had higher markers of bone turnover, lower areal bone mineral density at the radius by dual energy x-ray absorptiometry, and lower cortical and trabecular volumetric bone mineral density and impaired trabecular microarchitecture. Over time, acidosis was associated with opposing cortical and trabecular effects: cortical expansion but trabecular deterioration. Bone-tissue analyses showed reduced tissue mineral density with increased heterogeneity of calcium distribution in acidotic participants. CONCLUSIONS: MA is associated with multiple impairments in bone quality. Future work should examine whether correction of acidosis improves bone quality and strength in patients with CKD.

[Comparison of acquired immure deficiency syndrome-related knowledge and behavior between persons with and without human immunodeficiency virus- infection among young male students who have sex with men].

OBJECTIVE: To understand the differences between young male students who have sex with men (MSM) with and without human immunodeficiency virus (HIV)-infection in acquired immure deficiency syndrome (AIDS)-related knowledge and behavior, and to provide a scientific reference to make targeted and effective measures in AIDS prevention. METHODS: Using snow balling sampling combined with participants' referral, we conducted a questionnaire survey among 548 young MSM students (in whom there were both HIV-positive and HIV-negative) in Harbin, Tianjin, Xi'an, and Chongqing cities from April 2017 to March 2018. The chi-square test and binary Logistic regression were used to compare the differences in AIDS-related knowledge and behavior between males with and without HIV-infection. RESULTS: A total of 583 questionnaires were obtained, of which 548 were valid, with an effective rate of 94.0%. Having a junior college education or below (P=0.002), a monthly consumption level of less than 2 000 RMB (P=0.021), and living off campus (P=0.004) were associated with being tested positive for HIV. In any period of schooling, receiving AIDS prevention education was a protective factor for HIV infection [Primary school OR=0.203 (0.073－0.561), junior high school OR=0.287 (0.142－0.581), senior high school OR=0.271 (0.142－0.518), and university OR=0.322 (0.168－0.616)]. There was no statistical difference between HIV positive and negative young MSM students in the cognition of "AIDS-related Knowledge for Public"(P=0.907) and "AIDS-related Knowledge for Youth"(P=0.782), with the awareness rate all about 90%. There was a statistical difference in the need for some specific knowledge (For "AIDS prevention and treatment policy", P=0.012, for "Ways to identify and prevent high-risk sexual behavior", P < 0.001). HIV-positive males had a younger age of first sexual activity (P=0.006), had more sexual partners in the early (P < 0.001) and had lower frequency of condom use (P < 0.001). However, there was no statistical difference in the later number of sexual partners (P=0.247) and the frequency of condom use (For regular sex partners, P=0.735, and for casual sex partners, P=0.765), which might be related to the change of sexual behavior characteristics caused by HIV infection (For regular sex partners, P < 0.001, and for casual sex partners, P=0.006). CONCLUSION: There was no statistical difference between HIV positive and negative young MSM students in the cognition of "AIDS-related Knowledge for Public" and "AIDS-related Knowledge for Youth", which were both lower than 95% required by the state. However, the specificity in the knowledge needs was certainly shown. There was no significant difference in the recent sexual behavior between the two groups, but HIV positive students were more likely to have high-risk sexual behaviors in the early stage, so we should strengthen and move forward the sex education and AIDS prevention education with adjusted contents, and prevent high-risk sexual behaviors within young MSM students in the early stage.

Correction to: Differences in bone quality and strength between Asian and Caucasian young men.

The second name of the ninth author, X.E. Guo, was incorrectly coded as part of his surname. The publisher apologises for the inconvenience caused.

Abnormal microarchitecture and stiffness in postmenopausal women using chronic inhaled glucocorticoids.

Postmenopausal (PM) women using inhaled glucocorticoids (IGCs) had substantial abnormalities in volumetric BMD (vBMD), microarchitecture, and stiffness using high resolution peripheral computed tomography (HRpQCT) compared to age- and race-matched controls. Abnormalities were most severe at the radius. These preliminary results suggest that there may be major, heretofore unrecognized, skeletal deficits in PM women using IGCs. INTRODUCTION: While oral glucocorticoids are well recognized to have destructive skeletal effects, less is known about the effects of IGCs. The detrimental skeletal effects of IGCs may be greatest in PM women, in whom they compound negative effects of estrogen loss and aging. The goal of this study was to evaluate microarchitecture and stiffness in PM women using chronic IGCs. METHODS: This case-control study compared PM women using IGCs for ≥ 6 months (n = 20) and controls matched for age and race/ethnicity (n = 60). Skeletal parameters assessed included areal BMD (aBMD) by DXA, trabecular and cortical vBMD and microarchitecture by HRpQCT of the radius and tibia, and whole bone stiffness by finite element analysis. RESULTS: By DXA, mean values in both groups were in the osteopenic range; hip aBMD was lower in IGC users (P < 0.04). By HRpQCT, IGC users had lower total, cortical, and trabecular vBMD at both radius and tibia (all P < 0.05). IGC users had lower cortical thickness, lower trabecular number, greater trabecular separation and heterogeneity at the radius (all P < 0.03), and greater heterogeneity at the tibia (P < 0.04). Whole bone stiffness was lower in IGC users at radius (P < 0.03) and tended to be lower at the tibia (P = 0.09). CONCLUSIONS: PM women using IGCs had substantial abnormalities in vBMD, microarchitecture, and stiffness compared to controls. These abnormalities were most severe at the radius. These preliminary results suggest that there may be major, heretofore unrecognized, skeletal deficits in PM women using IGCs.

In vivo assessment of bone structure and estimated bone strength by first- and second-generation HR-pQCT.

UNLABELLED: Bone strength is dependent on bone density and microstructure. High-resolution peripheral quantitative computed tomography (HR-pQCT) can measure microstructure but is somewhat limited due to its resolution. We compared a new HR-pQCT scanner to existing technology and found very good agreement for most parameters. This study will be important when interpreting results from different devices. INTRODUCTION: Recently, a second-generation HR-pQCT scanner (XCT2) has been developed with a higher nominal isotropic resolution (61 µm) compared to the first-generation device (XCT1, 82 µm). It is unclear how in vivo measurements from these two devices compare. In this study, we obtained and analyzed in vivo XCT1 and XCT2 measurements of bone microarchitecture and estimated strength. METHODS: We scanned 51 adults (16 men and 35 women, age 44.8 ± 16.0) on both XCT2 and XCT1 on the same day. We first compared XCT1 and XCT2 measurements obtained using their respective standard patient protocols. In XCT1, microarchitecture parameters were derived, while XCT2 measurements were directly measured. We also compared XCT2-D with XCT1 by finding the overlapping regions of interest and using the standard patient protocol for XCT1. RESULTS: We obtained excellent agreement between XCT1 and XCT2 for most of the volumetric bone mineral density (vBMD), trabecular and cortical measurements (All R (2) > 0.820) except for cortical porosity at the radius (R (2) = 0.638), trabecular number (R (2) = 0.694, 0.787) and trabecular thickness (R (2) = 0.569, 0.527) at both radius and tibia, respectively. XCT1 and XCT2-D measurements also had excellent agreement for most of the measurements (all R (2) > 0.870) except trabecular number (R (2) = 0.524, 0.706), trabecular thickness (R (2) = 0.758, 0.734) at both radius and tibia, respectively, and trabecular separation (R (2) = 0.656) at the radius. CONCLUSION: While some caution should be exercised for parameters that are more dependent on image resolution, results from our study indicate that second-generation scans can be compared to more widely available first-generation data and may be beneficial for multicenter and longitudinal studies using both scanner generations.

Bone turnover and articular cartilage differences localized to subchondral cysts in knees with advanced osteoarthritis.

OBJECTIVE: To investigate changes in bone structure, turnover, and articular cartilage localized in subchondral bone cyst (SBC) regions associated with knee osteoarthritis (OA). METHODS: Tibial plateaus (n = 97) were collected from knee OA patients during total knee arthroplasty (TKA). SBCs were identified using micro-computed tomography, and the specimens were divided into non-cyst (n = 25) and bone cyst (n = 72) groups. Microstructure of subchondral bone was assessed using bone volume fraction (BV/TV), trabecular number (Tb.N), structure model index (SMI) and bone mineral density (BMD). In bone cyst group, the cyst subregion, which contained at least one cyst, and the peri-cyst subregion, which contained no cysts, were further selected for microstructure analysis. Articular cartilage damage was estimated using the Osteoarthritis Research Society International (OARSI) score. The numbers of TRAP(+) osteoclasts, Osterix(+) osteoprogenitors, Osteocalcin(+) osteoblasts and expression of SOX9 were evaluated by immunohistochemistry. RESULTS: Bone cyst group presented higher BV/TV, Tb.N and SMI at subchondral bone than non-cyst group. Furthermore, cyst subregion displayed increased BV/TV and Tb.N but lower BMD and SMI than peri-cyst subregion. Histology revealed a higher OARSI score in bone cyst group. SBC exhibited a weak relationship with BV/TV, etc. The numbers of TRAP(+) osteoclasts, Osterix(+) osteoprogenitors, Osteocalcin(+) osteoblasts and expression of SOX9, were higher in bone cyst group. CONCLUSION: SBCs within knee OA are characterized by focally increased bone turnover, altered bone structure and more severe articular cartilage damage. The increased bone turnover possibly contributes to altered bone structure localized in SBC areas, and thus aggravates articular cartilage degeneration.

Novel small molecules disrupting Hec1/Nek2 interaction ablate tumor progression by triggering Nek2 degradation through a death-trap mechanism.

Hec1 (highly expressed in cancer 1) or Nek2 (NIMA-related kinase 2) is often overexpressed in cancers with poor prognosis. Both are critical mitotic regulators, and phosphorylation of Hec1 S165 by Nek2 is required for proper chromosome segregation. Therefore, inactivation of Hec1 and Nek2 by targeting their interaction with small molecules represents an ideal strategy for tackling these types of cancers. Here we showed that new derivatives of INH (inhibitor for Nek2 and Hec1 binding) bind to Hec1 at amino acids 394-408 on W395, L399 and K400 residues, effectively blocking Hec1 phosphorylation on S165 by Nek2, and killing cancer cells at the nanomolar range. Mechanistically, the D-box (destruction-box) region of Nek2 specifically binds to Hec1 at amino acids 408-422, immediately adjacent to the INH binding motif. Subsequent binding of Nek2 to INH-bound Hec1 triggered proteasome-mediated Nek2 degradation, whereas the Hec1 binding defective Nek2 mutant, Nek2 R361L, resisted INH-induced Nek2 degradation. This finding unveils a novel drug-action mechanism where the binding of INHs to Hec1 forms a virtual death-trap to trigger Nek2 degradation and eventually cell death. Furthermore, analysis of the gene expression profiles of breast cancer patient samples revealed that co-elevated expressions of Hec1 and Nek2 correlated with the shortest survival. Treatment of mice with this kind of tumor with INHs significantly suppressed tumor growth without obvious toxicity. Taken together, the new INH derivatives are suitable for translation into clinical application.

A trabecular plate-like phenotype is overrepresented in Chinese-American versus Caucasian women.

UNLABELLED: This study used extreme phenotype selection to define two trabecular bone phenotypes in a cohort of Chinese-American and Caucasian women. A trabecular plate-predominant phenotype is more common in Chinese-Americans while the rod-predominant phenotype is more typical of Caucasians. The robustness of these phenotypic associations with respect to lifestyle factors suggests that this trait may have a genetic basis and that these phenotypes can be utilized in future genetic studies. INTRODUCTION: Compared to Caucasians, Chinese-Americans have more plate-like trabecular bone when measured by individual trabecula segmentation (ITS). These findings suggest a phenotypic difference between the races, which may be amenable to genetic analysis. We sought to identify a single ITS plate trait to pursue in genetic studies by conducting an extreme phenotype selection strategy to numerically define two distinct phenotypes-plate-like and rod-like-and determine whether the selected phenotypic associations were independent of lifestyle factors in order to conduct future genetic studies. METHODS: A previously described cohort of 146 Chinese-American and Caucasian women with high-resolution peripheral quantitative computed tomography imaging and ITS analyses were studied with logistic regression and receiver operator characteristic analyses. RESULTS: The tibial plate-to-rod (TPR) ratio was the best ITS discriminator of race. Using extreme phenotypic selection, two TPR ratio phenotypes were defined numerically: plate-like as a TPR ratio value in the highest quartile (≥1.336) and rod-like as a TPR ratio value in the lowest quartile (≤0.621). Women with a plate-like phenotype were 25.7 times more likely (95 % CI 7.3-90.1) to be Chinese-American than women with rod-like morphology. After controlling for constitutional and lifestyle covariates, women in the highest vs. lowest TPR ratio quartile were 85.0 times more likely (95 % CI 12.7-568.0) to be Chinese-American. CONCLUSION: Using extreme phenotype selection, we defined a plate- and rod-like trabecular bone phenotype for the TPR ratio trait. The former phenotype is more common in Chinese-American women, while the latter is more typical of Caucasian women. The robustness of these phenotypic associations after controlling for differences in constitution and lifestyle suggest that the TPR ratio may have a genetic basis and that the extreme phenotypes defined in this analysis can be utilized for future studies.

Effects of low intensity vibration on bone and muscle in rats with spinal cord injury.

UNLABELLED: Spinal cord injury (SCI) causes rapid and marked bone loss. The present study demonstrates that low-intensity vibration (LIV) improves selected biomarkers of bone turnover and gene expression and reduces osteoclastogenesis, suggesting that LIV may be expected to benefit to bone mass, resorption, and formation after SCI. INTRODUCTION: Sublesional bone is rapidly and extensively lost following spinal cord injury (SCI). Low-intensity vibration (LIV) has been suggested to reduce loss of bone in children with disabilities and osteoporotic women, but its efficacy in SCI-related bone loss has not been tested. The purpose of this study was to characterize effects of LIV on bone and bone cells in an animal model of SCI. METHODS: The effects of LIV initiated 28 days after SCI and provided for 15 min twice daily 5 days each week for 35 days were examined in female rats with moderate severity contusion injury of the mid-thoracic spinal cord. RESULTS: Bone mineral density (BMD) of the distal femur and proximal tibia declined by 5 % and was not altered by LIV. Serum osteocalcin was reduced after SCI by 20 % and was increased by LIV to a level similar to that of control animals. The osteoclastogenic potential of bone marrow precursors was increased after SCI by twofold and associated with 30 % elevation in serum CTX. LIV reduced the osteoclastogenic potential of marrow precursors by 70 % but did not alter serum CTX. LIV completely reversed the twofold elevation in messenger RNA (mRNA) levels for SOST and the 40 % reduction in Runx2 mRNA in bone marrow stromal cells resulting from SCI. CONCLUSION: The findings demonstrate an ability of LIV to improve selected biomarkers of bone turnover and gene expression and to reduce osteoclastogenesis. The study indicates a possibility that LIV initiated earlier after SCI and/or continued for a longer duration would increase bone mass.

Mitochondrial genome instability resulting from SUV3 haploinsufficiency leads to tumorigenesis and shortened lifespan.

Mitochondrial dysfunction has been a hallmark of cancer. However, whether it has a causative role awaits to be elucidated. Here, using an animal model derived from inactivation of SUV3, a mitochondrial helicase, we demonstrated that mSuv3+/- mice harbored increased mitochondrial DNA (mtDNA) mutations and decreased mtDNA copy numbers, leading to tumor development in various sites and shortened lifespan. These phenotypes were transmitted maternally, indicating the etiological role of the mitochondria. Importantly, reduced SUV3 expression was observed in human breast tumor specimens compared with corresponding normal tissues in two independent cohorts. These results demonstrated for the first time that maintaining mtDNA integrity by SUV3 helicase is critical for cancer suppression.

Assessment of trabecular and cortical architecture and mechanical competence of bone by high-resolution peripheral computed tomography: comparison with transiliac bone biopsy.

UNLABELLED: We compared microarchitecture and mechanical competence parameters measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite-element analysis of radius and tibia to those measured by histomorphometry, micro-CT, and finite-element analysis of transiliac bone biopsies. Correlations were weak to moderate between parameters measured on biopsies and scans. INTRODUCTION: HR-pQCT is a new imaging technique that assesses trabecular and cortical bone microarchitecture of the radius and tibia in vivo. The purpose of this study was to determine the extent to which microarchitectural variables measured by HR-pQCT reflect those measured by the "gold standard," transiliac bone biopsy. METHODS: HR-pQCT scans (Xtreme CT, Scanco Medical AG) and iliac crest bone biopsies were performed in 54 subjects (aged 39 +/- 10 years). Biopsies were analyzed by 2D quantitative histomorphometry and 3D microcomputed tomography (microCT). Apparent Young's modulus, an estimate of mechanical competence or strength, was determined by micro-finite-element analysis (microFE) of biopsy microCT and HR-pQCT images. RESULTS: The strongest correlations observed were between trabecular parameters (bone volume fraction, number, separation) measured by microCT of biopsies and HR-pQCT of the radius (R 0.365-0.522; P < 0.01). Cortical width of biopsies correlated with cortical thickness by HR-pQCT, but only at the tibia (R = 0.360, P < 0.01). Apparent Young's modulus calculated by microFE of biopsies correlated with that calculated for both radius (R = 0.442; P < 0.001) and tibia (R = 0.380; P < 0.001) HR-pQCT scans. CONCLUSIONS: The associations between peripheral (HR-pQCT) and axial (transiliac biopsy) measures of microarchitecture and estimated mechanical competence are significant but modest.

Proteoglycans and mechanical behavior of condylar cartilage.

Mandibular condylar cartilage functions as the load-bearing, shock-absorbing, lubricating material in temporomandibular joints. Little is known about the precise nature of the biomechanical characteristics of this fibro-cartilaginous tissue. We hypothesized that the fixed charge density associated with proteoglycans that introduces an osmotic pressure inside condylar cartilage will significantly increase the tissue's apparent stiffness. Micro-indentation creep tests were performed on porcine TMJ condylar cartilage at 5 different regions-anterior, posterior, medial, lateral, and central-in physiologic and hypertonic solutions. The intrinsic and apparent mechanical properties, including aggregate modulus, shear modulus, and permeability, were calculated by indentation test data and the biphasic theory. The apparent properties (with osmotic effect) were statistically higher than those of the intrinsic solid matrix (without osmotic effect). Regional variations in fixed charge density, permeability, and mechanical modulus were also calculated for condylar surface. The present results provide important quantitative data on the biomechanical properties of TMJ condylar cartilage.

Diffusion-based MR methods for bone structure and evolution.

A new approach to MR trabecular bone characterization is presented. This method probes the diffusion of spins through internal magnetic field gradients due to the susceptibility contrast between the bone and water (or marrow) phases. The resulting spin magnetization decay encodes properties of the underlying structure. This method, termed decay due to diffusion in the internal field (DDIF), is well established as a probe of pore size and structure. In the present work its application is shown for in vitro experiments on excised bovine tibiae samples. A comparison with pulsed field gradient (PFG) measurement of restricted diffusion shows a strong correlation of DDIF with the surface-to-volume ratio (SVR) of bones. Calculation of the internal magnetic field within the bone structure also supports this interpretation. These NMR measurements compare well with the image analysis from microscopic computed tomography (muCT). The SVR is not accessible in the clinically standard densitometry measurements, and provides vital information on bone strength and therefore on its fracture risk. The DDIF and PFG methods derive this information from a straightforward pulse sequence that does not employ either high applied field gradients or microimaging, and thus may have clinical potential.

Substrate modulation of osteoblast adhesion strength, focal adhesion kinase activation, and responsiveness to mechanical stimuli.

Osteoblast interactions with extracellular matrix (ECM) proteins are known to influence many cell functions, which may ultimately affect osseointegration of implants with the host bone tissue. Some adhesion-mediated events include activation of focal adhesion kinase, and subsequent changes in the cytoskeleton and cell morphology, which may lead to changes in adhesion strength and cell responsiveness to mechanical stimuli. In this study we examined focal adhesion kinase activation (FAK), F-actin cytoskeleton reorganization, adhesion strength, and osteoblast responsiveness to fluid shear when adhered to type I collagen (ColI), glass, poly-L-lysine (PLL), fibronectin (FN), vitronectin (VN), and serum (FBS). In general, surfaces that bind cells through integrins (FN, VN, FBS) elicited the highest adhesion strength, FAK activation, and F-actin stress fiber formation after both 15 and 60 minutes of adhesion. In contrast, cells attached through non-integrin mediated means (PLL, glass) showed the lowest FAK activation, adhesion strength, and little F-actin stress fiber formation. When subjected to steady fluid shear using a parallel plate flow chamber, osteoblasts plated on FN released significantly more PGE2 compared to those on glass. In contrast, PGE2 release of osteoblasts attached to FN or glass was not different in the absence of fluid shear, suggesting that differences in binding alone are insufficient to alter PGE2 secretion. The increased adhesion strength as well as PGE2 secretion of osteoblasts adhered via integrins may be due to increased F-actin fiber formation, which leads to increased cell stiffness.

The influence of the fixed negative charges on mechanical and electrical behaviors of articular cartilage under unconfined compression.

Unconfined compression test has been frequently used to study the mechanical behaviors of articular cartilage, both theoretically and experimentally. It has also been used in explant and gel-cell-complex studies in tissue engineering. In biphasic and poroelastic theories, the effect of charges fixed on the proteoglycan macromolecules in articular cartilage is embodied in the apparent compressive Young's modulus and the apparent Poisson's ratio of the tissue, and the fluid pressure is considered to be the portion above the osmotic pressure. In order to understand how proteoglycan fixed charges might affect the mechanical behaviors of articular cartilage, and in order to predict the osmotic pressure and electric fields inside the tissue in this experimental configuration, it is necessary to use a model that explicitly takes into account the charged nature of the tissue and the flow of ions within its porous interstices. In this paper, we used a finite element model based on the triphasic theory to study how fixed charges in the porous-permeable soft tissue can modulate its mechanical and electrochemical responses under a step displacement in unconfined compression. The results from finite element calculations showed that: 1) A charged tissue always supports a larger load than an uncharged tissue of the same intrinsic elastic moduli. 2) The apparent Young's modulus (the ratio of the equilibrium axial stress to the axial strain) is always greater than the intrinsic Young's modulus of an uncharged tissue. 3) The apparent Poisson's ratio (the negative ratio of the lateral strain to the axial strain) is always larger than the intrinsic Poisson's ratio of an uncharged tissue. 4) Load support derives from three sources: intrinsic matrix stiffness, hydraulic pressure and osmotic pressure. Under the unconfined compression, the Donnan osmotic pressure can constitute between 13%-22% of the total load support at equilibrium. 5) During the stress-relaxation process following the initial instant of loading, the diffusion potential (due to the gradient of the fixed charge density and the associated gradient of ion concentrations) and the streaming potential (due to fluid convection) compete against each other. Within the physiological range of material parameters, the polarity of the electric potential depends on both the mechanical properties and the fixed charge density (FCD) of the tissue. For softer tissues, the diffusion effects dominate the electromechanical response, while for stiffer tissues, the streaming potential dominates this response. 6) Fixed charges do not affect the instantaneous strain field relative to the initial equilibrium state. However, there is a sudden increase in the fluid pressure above the initial equilibrium osmotic pressure. These new findings are relevant and necessary for the understanding of cartilage mechanics, cartilage biosynthesis, electromechanical signal transduction by chondrocytes, and tissue engineering.

Electrical signals for chondrocytes in cartilage.

An important step toward understanding signal transduction mechanisms modulating cellular activities is the accurate predictions of the mechanical and electro-chemical environment of the cells in well-defined experimental configurations. Although electro-kinetic phenomena in cartilage are well known, few studies have focused on the electric field inside the tissue. In this paper, we present some of our recent calculations of the electric field inside a layer of cartilage (with and without cells) in an open circuit one-dimensional (1D) stress relaxation experiment. The electric field inside the tissue derives from the streaming effects (streaming potential) and the diffusion effect (diffusion potential). Our results show that, for realistic cartilage material parameters, due to deformation-induced inhomogeneity of the fixed charge density, the two potentials compete against each other. For softer tissue, the diffusion potential may dominate over the streaming potential and vice versa for stiffer tissue. These results demonstrate that for proper interpretation of the mechano-electrochemical signal transduction mechanisms, one must not ignore the diffusion potential.