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PubMed1996

Phylogeny and taxonomy of mesophilic Methanococcus spp. and comparison of rRNA, DNA hybridization, and phenotypic methods.

The phylogeny and taxonomy of the mesophilic methane-producing archaea of the order Methanococcales were examined by DNA relatedness, 16S rRNA sequence analysis, cellular protein patterns, and phenotypic methods. The mesophilic species Methanococcus maripaludis, Methanococcus vannielii, Methanococcus voltaei, and "Methanococcus aeolicus" formed a deep group with 5 to 30% DNA relatedness and 92 to 96% 16S rRNA sequence similarity. Twenty-two additional isolates and Methanococcus deltae were similar to the type strain of either M. voltaei or M. maripaludis. Two isolates, strains A2 and A3, exhibited 37% DNA relatedness and 99.2% 16S rRNA sequence similarity to M. voltaei PS(T) (T = type strain). In the absence of phenotypic differences, these organisms were assigned to M. voltaei. Similarly, four autotrophic isolates, strains C5, C6, C7, and C8, exhibited 54 to 69% DNA relatedness and 99.2% 16S rRNA sequence similarity to M. maripaludis JJT and were assigned to M. Maripaludis. While these isolates were sufficiently genetically diverse to justify classification in novel species, few differences were apparent in the phenotypic properties available for measurement. Thus, the phenotypic properties of these lithotrophic archaea were highly conserved and poor indicators of genetic diversity. Partial sequencing of about 200 bases of both the 16S and 23S rRNAs of the isolates demonstrated allelic diversity within methanococcal species. This allelic diversity did not correlate with diversity measured by DNA relatedness, cellular protein pattern, and other methods. Similarly, antisera to whole cells of the type strains did not cross-react strongly to whole cells of strains that were genetically similar, and serological cross-reactivity was not a useful taxonomic method for methanococci. Lastly, on the basis of the results of 16S rRNA sequence analyses and biochemical data, the ancestor of the mesophilic methanococci may have been an autotrophic thermophile.

Bacterial Proteins↗
PubMedDate not supplied

Molecular, histologic, and gross phenotype of skin wound healing in red Duroc pigs reveals an abnormal healing phenotype of hypercontracted, hyperpigmented scarring.

This study examined dermal wound healing in juvenile red Duroc pigs and determined that these animals exhibit a unique healing phenotype at multiple levels. Gross and histologic analysis revealed that full-thickness and deep dermal (1.8 mm deep) wounds both heal via formation of hypercontracted, hyperpigmented scars. Molecular analysis using reverse-transcriptase polymerase chain reaction and porcine-specific primer sets revealed that types I and III collagen, heat shock protein 47, bone morphogenetic protein-1, several proteoglycans, and tissue inhibitor of metalloproteinases 1-3 all showed a unique biphasic pattern of mRNA expression compared to previous results with Yorkshire pigs. This pattern was characterized by an initial peak of expression early after wounding, followed by a return to near-normal levels by days 28-42, and then a second increase in mRNA levels at days 56-70. The second phase of increased gene expression correlated with an increased collagen deposition as observed by picrosirius red staining and polarizing light microscopy. Reverse-transcriptase polymerase chain reaction analysis also revealed a prolonged expression of matrix metalloproteinase-2 compared to previous findings in the Yorkshire strain. Further characterization of the genetics and molecular biology associated with the red Duroc phenotype may provide insight into aberrant human wound healing.

Animals↗
PubMed2003

Mollaret's meningitis: cytopathologic analysis of fourteen cases.

Mollaret's meningitis (MM) is a rare disease of benign nature characterized by recurrent episodes of aseptic meningitis. Cerebrospinal fluid (CSF) examination remains the sole diagnostic modality. Eighteen CSF samples from 14 patients were studied along with the clinical data. Specimens were prepared by cytocentrifugation and Millipore filtration and were stained with Diff-Quik and Papanicolaou stains. Eight patients were men and six were women, with an age range of 17-74 yr (mean age 37 yr). Most common clinical presentation was recurrent episodes of headaches and photophobia followed by a sustained mild fever lasting 5-7 days. The CSF showed markedly increased cellularity with pleocytosis. The differential count showed predominant monocytosis ranging from 84% to 100% (mean 96). In our series, two patients had herpes simplex virus type 2 (HSV-2) DNA detected by polymerase chain reaction (PCR) in the CSF. The monocytes were seen predominantly singly, but three cases showed a strong tendency to aggregate in small groups. Phenotypically, these cells had bean-shaped bilobed nuclei as well as multiple deep nuclear clefts depicting the so-called "footprint" appearance. In four cases, multiple blunt-tipped cytoplasmic pseudopods were noted. Degenerated monocytes with the appearance of the so-called "ghost cells" were noted in one-half of the cases. Background cells were mostly small mature lymphocytes; however, one-half of cases showed a significant amount of plasma cells and/or polymorphonuclear leukocytes (PMNs). Lysed blood with hemosiderin-laden macrophages and numerous leptomeningeal cells were seen in two cases. CSF examination of MM presents a spectrum of cytomorphologic features. When interpreted in light of the appropriate clinical setting. the latter, although nonspecific, provides an accurate diagnosis. The differential diagnosis includes various degenerative, inflammatory/infectious, and lymphoproliferative disorders of the central nervous system.

Adolescent↗
PubMed2005

GITR overexpression on CD4+CD25+ HTLV-1 transformed cells: detection by massively parallel signature sequencing.

HTLV-I is the etiologic agent of adult T-cell leukemia (ATL), a fatal T-cell malignancy that is associated with profound immunosuppression. In this study, comprehensive gene expression profiling was performed using massively parallel signature sequencing (MPSS) to investigate virus-host interactions in acutely HTLV-1 transformed cells. The analysis revealed the modulation of numerous genes across different functional classes, many of which have not been previously implicated in HTLV-1 transformation or ATL. Differences in the transcriptomes of transformed cell lines were observed that have provided clues on how different clonal populations of cells respond to virus transformation. Quantitation of HTLV-1 transcription was possible, thus making MPSS a useful tool to study emerging pathogens and unknown microbial causes of human diseases. Importantly, overexpression of GITR, an activation marker that has not been previously reported to be upregulated by HTLV-1-infection or in transformed/leukemic cells and that is associated with the suppressor phenotype of CD4+CD25+ regulatory T-cells (Tregs), was also observed. The deep and quantitative gene expression profile generated by MPSS should provide additional leads for discovery research that can be applied to better understand the pathobiology of HTLV-1 transformation and ATL as well as to developing new therapies.

CD4 Antigens↗
PubMed2003

Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction.

OBJECTIVES: We evaluated the role of Cypher/ZASP in the pathogenesis of dilated cardiomyopathy (DCM) with or without isolated non-compaction of the left ventricular myocardium (INLVM). BACKGROUND: Dilated cardiomyopathy, characterized by left ventricular dilation and systolic dysfunction with signs of heart failure, is genetically transmitted in 30% to 40% of cases. Genetic heterogeneity has been identified with mutations in multiple cytoskeletal and sarcomeric genes causing the phenotype. In addition, INLVM with a hypertrophic dilated left ventricle, ventricular dysfunction, and deep trabeculations, is also inherited, and the genes identified to date differ from those causing DCM. Cypher/ZASP is a newly identified gene encoding a protein that is a component of the Z-line in both skeletal and cardiac muscle. METHODS: Diagnosis of DCM was performed by echocardiogram, electrocardiogram, and physical examination. In addition, levels of the muscular isoform of creatine kinase were measured to evaluate for skeletal muscle involvement. Cypher/ZASP was screened by denaturing high performance liquid chromatography (DHPLC) and direct deoxyribonucleic acid sequencing. RESULTS: We identified and screened 100 probands with left ventricular dysfunction. Five mutations in six probands (6% of cases) were identified in patients with familial or sporadic DCM or INLVM. In vitro studies showed cytoskeleton disarray in cells transfected with mutated Cypher/ZASP. CONCLUSIONS: These data suggest that mutated Cypher/ZASP can cause DCM and INLVM and identify a mechanistic basis.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Vibrio diabolicus sp. nov., a new polysaccharide-secreting organism isolated from a deep-sea hydrothermal vent polychaete annelid, Alvinella pompejana.

A deep-sea, facultatively anaerobic, heterotrophic, mesophilic new organism was isolated from the polychaete annelid Alvinella pompejana collected from a deep-sea hydrothermal field in the East Pacific Rise. On the basis of phenotypic characteristics, phylogenetic analyses, and DNA-DNA relatedness, this organism was identified as a new species of the genus Vibrio, for which the name Vibrio diabolicus is proposed. In batch cultures in the presence of glucose, this organism produced an innovative exopolysaccharide. This polymer had high contents of both uronic acids and hexosamines and was similar to other polysaccharides with interesting biological activities.

Animals↗
PubMed2000

Type 2 segmental manifestation of Hailey-Hailey disease: poor therapeutic response to dermabrasion is due to severe involvement of adnexal structures.

In autosomal dominant skin conditions, two different types of segmental manifestation can be distinguished. Type 1 represents heterozygosity for a postzygotic mutation, resulting in a degree of severity similar to that of the nonmosaic phenotype. Type 2 reflects loss of heterozygosity and shows an excessively pronounced involvement superimposed on the ordinary nonsegmental phenotype. We describe the clinical, histopathological and therapeutic aspects of the first case of type 2 segmental manifestation of Hailey-Hailey disease (HHD). A 24-year-old woman with a family history of HHD comprising four generations, presented with lesions of erythema and blistering arranged in a unilateral pattern following the lines of Blaschko. The disorder was first noted at the age of 3 months. At the age of 24 years, additional scattered symmetrical lesions involving the axillary and inguinal folds were noted. Histopathological examination of the severely involved linear skin areas revealed pronounced acantholysis within the deep adnexal structures, whereas clinically unaffected skin showed the typical histopathological features of the heterozygous phenotype with suprabasal clefting and acantholysis sparing the adnexae. Dermabrasion was performed in the areas of segmental involvement. During a follow-up period of one year, no recurrence was noted, but 18 months after dermabrasion a recurrence was present in the left submammary and left perianal regions. This therapeutic resistance to dermabrasion may be explained by the presence of acantholysis within the adnexal structures of the skin as found in type 2 segmental HHD.

Acantholysis↗
PubMed1996

The zebrafish epiboly mutants.

Epiboly, the enveloping of the yolk cell by the blastoderm, is the first zebrafish morphogenetic movement. We isolated four mutations that affect epiboly: half baked, avalanche, lawine and weg. Homozygous mutant embryos arrest the vegetal progress of the deep cells of the blastoderm; only the yolk syncytial layer of the yolk cell and the enveloping layer of the blastoderm reach the vegetal pole of the embryo. The mutations half baked, avalanche and lawine produce a novel dominant effect, termed a zygotic-maternal dominant effect: heterozygous embryos produced from heterozygous females slow down epiboly and accumulate detached cells over the neural tube; a small fraction of these mutant individuals are viable. Heterozygous embryos produced from heterozygous males crossed to homozygous wild-type females complete epiboly normally and are completely viable. Additionally, embryos heterozygous for half baked have an enlarged hatching gland, a partial dominant phenotype. The phenotypes of these mutants demonstrate that, for the spreading of cells during epiboly, the movement of the deep cells of the blastoderm require the function of genes that are not necessary for the movement of the enveloping layer or the yolk cell. Furthermore, the dominant zygotic-maternal effect phenotypes illustrate the maternal and zygotic interplay of genes that orchestrate the early cell movements of the zebrafish.

Animals↗
PubMed2004

Is insulin resistance an essential component of PCOS?: The endometriosis syndromes: a clinical classification in the presence of aetiological confusion and therapeutic anarchy.

Clinical confusion and inappropriate management continues to surround endometriosis. It is poorly recognized that the disorder can exist in two different morphological forms that have different symptoms, signs and prognosis. Earlier classification systems have been useful for research but are of limited value in aiding day-to-day management. In the clinic, two discrete phenotypes can be defined by the presence or absence of palpable nodules in the deep pelvis. Patients with such nodules with or without associated ovarian endometrioma usually have severe symptoms with significant risks of bowel and urinary tract involvement. The predominant histological feature of these lesions is extensive fibromuscular hyperplasia (adenomyoma). These patients will often need extensive surgical intervention. Patients without such palpable lesions usually have the classic superficial subperitoneal lesions with endometrial-like glands and stroma on histological examination. This group often has less severe symptoms and has little risk of developing serious associated problems. These lesions may be helped by medications and/or simple ablative surgery. It is suggested that these collections of symptoms and signs or syndromes be named after the pioneers who first described the lesions. Cullen's syndrome can be used to describe those patients with severe symptoms of endometriosis associated with palpable pelvic nodules. Sampson's syndrome can describe those with similar symptoms associated with a structurally normal pelvis.

Endometriosis↗
PubMed2003

The impact of larval predators and competitors on the morphology and fitness of juvenile treefrogs.

Studies of phenotypic plasticity typically focus on traits in single ontogenetic stages. However, plastic responses can be induced in multiple ontogenetic stages and traits induced early in ontogeny may have lasting effects. We examined how gray treefrog larvae altered their morphology in four different larval environments and whether different larval environments affected the survival, growth, development, and morphology of juvenile frogs at metamorphosis. We then reared these juveniles in terrestrial environments under high and low intraspecific competition to determine whether the initial differences in traits at metamorphosis affected subsequent survival and growth, whether the initial phenotypic differences converged over time, and whether competition in the terrestrial environment induced further phenotypic changes. Larval and juvenile environments both affected treefrog traits. Larval predators induced relatively deep tail fins and short bodies, but there was no impact on larval development. In contrast, larval competitors induced relatively short tails and long bodies, reduced larval growth, and slowed larval development. At metamorphosis, larval predators had no effect on juvenile growth or relative morphology while larval competitors produced juveniles that were smaller and possessed relatively shorter limbs and shorter bodies. After 1 month of terrestrial competition among the juvenile frogs, the initial differences in juvenile morphology did not converge. There were no differences in growth due to larval treatment but there were differences in survival. Individuals that experienced low competition as tadpoles experienced near perfect survival as juvenile frogs but individuals that experienced high competition as tadpoles suffered an 18% decrease in survival as juvenile frogs. There were also morphological responses to juvenile competition, but these changes appear to be due, at least in part, to allometric effects. Collectively, these results demonstrate that larval environments can have profound impacts on the traits and fitness of organisms later in ontogeny.

Adaptation, Physiological↗
PubMed2003

Cross-linked type I and type II collagenous matrices for the repair of full-thickness articular cartilage defects--a study in rabbits.

The physico-chemical properties of collagenous matrices may determine the tissue response after insertion into full-thickness articular cartilage defects. In this study, cross-linked type I and type II collagen matrices, with and without attached chondroitin sulfate, were implanted into full-thickness defects in the femoral trochlea of adolescent rabbits. The tissue response was evaluated 4 and 12 weeks after implantation by general histology and two semi-quantitative histological grading systems. Four weeks after implantation, type I collagenous matrices were completely filled with cartilage-like tissue. By contrast, type II collagenous matrices revealed predominantly cartilaginous tissue only at the superficial zone and at the interface of the matrix with the subchondral bone, leaving large areas of the matrix devoid of tissue. Attachment of chondroitin sulfate appeared to promote cellular ingrowth and cartilaginous tissue formation in both types of collagen matrices. Twelve weeks after implantation, the differences between the matrices were less pronounced. The deep parts of the subchondral defects were largely replaced by new bone with a concomitant degradation of the matrices. The original cartilage contours in defects with type I collagen-based matrices were repaired with fibro-cartilaginous tissue. Defects containing type II matrices showed an increase in the amount of superficial cartilage-like tissue. The original contour, however, was not completely restored in all animals, occasionally leaving a central depression or fissure. It is concluded that different types of collagen matrices induce different tissue responses in full-thickness articular cartilage defects. Type I collagen-based matrices are superior to guide progenitor cells from a subchondral origin into the defect. In type II collagen-based matrices cell migration is less, but invading cells are directed into a chondrocyte phenotype. Based on these observations it is suggested that a composite matrix consisting of a deep layer of type I collagen and a more superficial layer of type II collagen may be the matrix of choice for cartilage regeneration.

Animals↗
PubMed1998

Phenotypic antibiotic tolerance of Staphylococcus aureus in implant-related infections: relationship with in vitro colonization of artificial surfaces.

Antibiotic therapy of deep-seated staphylococcal infections, especially when they are associated with foreign implants, such as orthopedic prostheses and permanently inserted catheters, is a difficult challenge. Semi-synthetic penicillins, glycopeptides and quinolones are found effective when given prophylactically in clinical and experimental trials of implant-related infections, but are frequently poorly effective after implant-related infections are established. Thus, removal of the medical devices is often required to obtain cure. The failure of antibiotic therapy to cure staphylococcal foreign body infections may arise from a broad-spectrum phenotypic tolerance to different classes of antimicrobial agents, whose molecular basis and physiological mechanisms are poorly understood.

Journal Article↗
PubMed2006

Skin wound healing in the first generation (F1) offspring of Yorkshire and red Duroc pigs: evidence for genetic inheritance of wound phenotype.

Fibroproliferative scars in humans often demonstrate familial inheritance patterns, and genetics may contribute to healing and scarring. Genetic factors may also influence the scarring phenotype in a porcine model. Healing of full thickness excisional skin wounds in Yorkshire pigs closely resembles normal healing in humans, while identical wounds in red Duroc pigs form hypercontracted, hyperpigmented scars. The present study has evaluated the healing process in the first generation cross (F1) of red Duroc and Yorkshire pigs. Gross and histologic analysis revealed that the F1 animals exhibit an intermediate healing phenotype, with some features of each parent breed. F1 full thickness wounds were significantly hypercontracted and fibrotic, but apigmented. Analysis of mRNA expression patterns for a panel of relevant molecules (N=32) in the F1 animals revealed some similarities to each parent breed, as well as unique patterns for other molecules. Furthermore, a depth dependency to the healing response was observed at the gross, histologic, and molecular levels, with deep dermal wounds healing similar to Yorkshire wounds. These findings suggest that the genetic contribution to scar phenotype in this animal model is complex. However, the results indicate that further understanding in this model may provide insights into risk factors for hypertrophic scarring in human burn patients.

Animals↗
PubMed2025

Deep learning-based assessment of missense variants in the COG4 gene presented with bilateral congenital cataract.

OBJECTIVE: We compared the protein structure and pathogenicity of clinically relevant variants of the COG4 gene with AlphaFold2 (AF2), Alpha Missense (AM), and ThermoMPNN for the first time. METHODS AND ANALYSIS: The sequences of clinically relevant Cog4 missense variants (one novel identified p.Y714F and three pre-existing p.G512R, p.R729W and p.L769R from Uniprot Q9H9E3) were imported into AF2 for protein structural prediction, and the pathogenicity was estimated using AM and ThermoMPNN. Different pathogenicity metrics were aggregated with principal component analysis (PCA) and further analysed at three levels (amino acid position, substitution and post-translation) based on all possible Cog4 missense variants (n=14 915). RESULTS: Localised protein structural impact including change of conformation and amino acid polarity, breakage of hydrogen bond and salt-bridge, and formation of alpha-helix were identified among clinically relevant Cog4 variants. The global structural comparison with multidimensional scaling demonstrated variants with similar protein structures (AF2) tended to exhibit similar clinical and biological phenotypes. The Cog4 p.Y714F variant exhibited greater protein structural similarity to mutated Cog4 found in Saul‒Wilson syndrome (p.G512R) and shared similar clinical phenotype (congenital cataract and psychomotor retardation). PCA of included pathogenic metrics demonstrated p.Y714F occurred at a critical position in Cog4 amino acid sequence with disrupted post-translational phosphorylation. CONCLUSION: Deep learning algorithms, including AF2, AM and ThermoMPNN, can be useful for evaluating variant of uncertain significance (VUS) by structural and pathogenicity prediction. Despite classified as VUS (American College of Medical Genetics and Genomics criteria: PM1, PP4), the pathogenicity in this Cog4 variant cannot be ruled out and warrants further investigation.

Mutation, Missense↗
PubMed2025

A neural network model enables worm tracking in challenging conditions and increases signal-to-noise ratio in phenotypic screens.

High-resolution posture tracking of C. elegans has applications in genetics, neuroscience, and drug screening. While classic methods can reliably track isolated worms on uniform backgrounds, they fail when worms overlap, coil, or move in complex environments. Model-based tracking and deep learning approaches have addressed these issues to an extent, but there is still significant room for improvement in tracking crawling worms. Here we train a version of the DeepTangle algorithm developed for swimming worms using a combination of data derived from Tierpsy tracker and hand-annotated data for more difficult cases. DeepTangleCrawl (DTC) outperforms existing methods, reducing failure rates and producing more continuous, gap-free worm trajectories that are less likely to be interrupted by collisions between worms or self-intersecting postures (coils). We show that DTC enables the analysis of previously inaccessible behaviours and increases the signal-to-noise ratio in phenotypic screens, even for data that was specifically collected to be compatible with legacy trackers including low worm density and thin bacterial lawns. DTC broadens the applicability of high-throughput worm imaging to more complex behaviours that involve worm-worm interactions and more naturalistic environments including thicker bacterial lawns.

Caenorhabditis elegans↗
PubMed2005

Haptoglobin phenotype 2-2 as a potentially new risk factor for spontaneous venous thromboembolism.

BACKGROUND AND OBJECTIVES: Haptoglobin (Hp) is a plasma protein that binds free hemoglobin and thus prevents catalysis of reactive oxygen species by the Fenton reaction. A genetic polymorphism has been described that leads to the generation of two distinct alleles, Hp1 and Hp2, which define three major haptoglobin phenotypes, denoted Hp1-1, Hp2-1 and Hp2-2. Hp2-2 has been reported to be associated with the risk of atherosclerosis and coronary heart disease. In our study we investigated the association of haptoglobin genotype and phenotype with the risk of spontaneous venous thromboembolism (VTE). DESIGN AND METHODS: One hundred and twenty-eight patients with a history of spontaneous deep vein thrombosis (70 women, 58 men), 105 with spontaneous symptomatic pulmonary embolism (58 women, 47 men) and 122 healthy controls (60 women, 62 men) were enrolled. Haptoglobin levels were measured immunonephelometrically and phenotypes were detected by polyacrylamide gel electrophoresis and subsequent immunoblotting. RESULTS: The Hp2-2 phenotype was significantly more prevalent in patients (42%) than in controls (30%) and significantly increased the risk for VTE in univariable (odds ratio=1.6, 95% confidence interval [1.0-2.6], p=0.04) and multivariable analyses (odds ratio=1.9 [1.0-3.4], p=0.04). Hp2-2 (n=134) was associated with significantly lower haptoglobin levels (median=89.7 mg/dL) than Hp2-1 (n=170, median = 123.5 mg/dL, p<0.001) or Hp1-1 (n=51, median=142.8 mg/dL, p<0.001). INTERPRETATION AND CONCLUSIONS: Our study gives the first evidence that Hp2-2 represents a risk factor for spontaneous VTE, presumably through a pathophysiological mechanism similar to that in arterial disease.

Adult↗
PubMed1996

Variable antifungal susceptibility of wild-type Candida albicans phenotypes from neutropenic hosts.

The aim of the present study was to investigate the relationship between phenotypes of Candida albicans strains isolated from clinical specimens and susceptibility of the strains to two antifungal agents, itraconazole and fluconazole. Oropharyngeal, gastrointestinal tract, and urogenital tract specimens were collected from 131 neutropenic patients with Candida infection who had received no previous prophylactic treatment. The most frequent species isolated was Candida albicans, followed by Candida glabrata, Candida tropicalis, Candida krusei, and Candida parapsilosis. Each of the 44 Candida albicans strains recovered was found to express one of four phenotypes: smooth, irregular, fuzzy or stipple. Mean minimum inhibitory concentrations (MICs) of itraconazole and fluconazole as determined by the microdilution method and the E-test were consistently higher for Candida albicans strains expressing the stipple phenotype. The mean MICs for the four phenotypes of the Candida albicans strains ranged between 0.35 microgram/ml and 2.41 micrograms/ml for itraconazole and 2.78 micrograms/ml for fluconazole. Antifungal susceptibility of the stipple phenotype requires careful appraisal, especially in patients clinically unresponsive to azole chemotherapy or in cases of life-threatening, deep-seated Candida infections.

Analysis of Variance↗
PubMed2003

Modelling cartilage mechanobiology.

The growth, maintenance and ossification of cartilage are fundamental to skeletal development and are regulated throughout life by the mechanical cues that are imposed by physical activities. Finite element computer analyses have been used to study the role of local tissue mechanics on endochondral ossification patterns, skeletal morphology and articular cartilage thickness distributions. Using single-phase continuum material representations of cartilage, the results have indicated that local intermittent hydrostatic pressure promotes cartilage maintenance. Cyclic tensile strains (or shear), however, promote cartilage growth and ossification. Because single-phase material models cannot capture fluid exudation in articular cartilage, poroelastic (or biphasic) solid/fluid models are often implemented to study joint mechanics. In the middle and deep layers of articular cartilage where poroelastic analyses predict little fluid exudation, the cartilage phenotype is maintained by cyclic fluid pressure (consistent with the single-phase theory). In superficial articular layers the chondrocytes are exposed to tangential tensile strain in addition to the high fluid pressure. Furthermore, there is fluid exudation and matrix consolidation, leading to cell 'flattening'. As a result, the superficial layer assumes an altered, more fibrous phenotype. These computer model predictions of cartilage mechanobiology are consistent with results of in vitro cell and tissue and molecular biology experiments.

Animals↗