Differentiated activities of decorin and biglycan in the progression of post-traumatic osteoarthritis.

OBJECTIVE: To delineate the activities of decorin and biglycan in the progression of post-traumatic osteoarthritis (PTOA). DESIGN: Three-month-old inducible biglycan (BgniKO) and decorin/biglycan compound (Dcn/BgniKO) knockout mice were subjected to the destabilization of the medial meniscus (DMM) surgery to induce PTOA. The OA phenotype was evaluated by assessing joint structure and sulfated glycosaminoglycan (sGAG) staining via histology, surface collagen fibril nanostructure and calcium content via scanning electron microscopy, tissue modulus via atomic force microscopy-nanoindentation, as well as subchondral bone structure and meniscus ossification via micro-computed tomography. Outcomes were compared with previous findings in the inducible decorin (DcniKO) knockout mice. RESULTS: In the DMM model, BgniKO mice developed similar degree of OA as the control (0.44 [-0.18 1.05] difference in modified Mankin score), different from the more severe OA phenotype observed in DcniKO mice (1.38 [0.91 1.85] difference). Dcn/BgniKO mice exhibited similar histological OA phenotype as DcniKO mice (1.51 [0.97 2.04] difference vs control), including aggravated loss of sGAGs, salient surface fibrillation and formation of osteophyte. Meanwhile, Dcn/BgniKO mice showed further cartilage thinning than DcniKO mice, resulting in the exposure of underlying calcified tissues and aberrantly high surface modulus. BgniKO and Dcn/BgniKO mice developed altered subchondral trabecular bone structure in both Sham and DMM groups, while DcniKO and control mice did not. CONCLUSION: In PTOA, decorin plays a more crucial role than biglycan in regulating cartilage degeneration, while biglycan is more important in regulating subchondral bone structure. The two have distinct activities and modest synergy in the pathogenesis of PTOA.

Clinical characteristics of lupus enteritis in Japanese patients: the large intestine-dominant type has features of intestinal pseudo-obstruction.

This study was performed to investigate the clinical characteristics of lupus enteritis in Japanese patients with systemic lupus erythematosus (SLE). A total of 481 patients with SLE admitted to our hospital between 2001 and 2015 were retrospectively reviewed. Diagnosis of lupus enteritis was based on the following three criteria: (1) abdominal symptoms, (2) diffuse long-segment bowel thickening and (3) a requirement for glucocorticoid therapy. Lupus enteritis was identified in 17 patients (3.5%) and there were two distinct types: small intestine-dominant and large intestine-dominant. Significant differences between the two types were noted with respect to the age, frequency of biopsy-proven lupus nephritis, frequency of rectal involvement, maximum bowel wall thickness, and requirement for steroid pulse therapy. Among patients with large intestine-dominant lupus enteritis, 60% had extra-intestinal symptoms (hydroureter, bladder wall thickening, and bile duct dilatation) that are known complications of intestinal pseudo-obstruction. Two patients with large intestine-dominant lupus enteritis developed intestinal pseudo-obstruction either before or after diagnosis of lupus enteritis. Five patients (29%) developed recurrence during a median observation period of 7.2 years (1.4-14.4 years). In conclusion, large intestine-dominant lupus enteritis resembles intestinal pseudo-obstruction and these two diseases may have a common pathogenesis.

Housing and income effects on HIV-related health outcomes in the San Francisco Bay Area - findings from the SPNS transwomen of color initiative.

Transwomen of color are disproportionately impacted by HIV and may have worse health outcomes than other populations. This analysis was conducted to examine structural factors associated with poor health outcomes among transwomen of color living with HIV in the San Francisco Bay Area (N = 159). Univariate and multivariable analyses were conducted to determine if structural factors were associated with poor HIV-related health outcomes. A majority of participants were Black or African American (110/159, 69.2%), 32 (20.1%) identified their primary race/ethnicity as Hispanic or Latino/a or Spanish, and 17 (10.7%) identified as another race/ethnicity. Transwomen of color in our sample faced extreme structural barriers, including residential transience, extreme low income, high prevalence of running out of money in the last six months, high rates of food insecurity, high prevalence of income via entitlement programs, engagement in sex work and other illicit activities for income. Unstable housing was the structural factor most consistently associated with poor health outcomes along the HIV care continuum and may explain engagement in other sources of income generation. Interventions are needed that go beyond the individual and health care-level to address needs for housing and economic opportunities to improve HIV care outcomes among transwomen of color living with HIV in the San Francisco Bay Area.

Nanoindentation modulus of murine cartilage: a sensitive indicator of the initiation and progression of post-traumatic osteoarthritis.

OBJECTIVE: This study aims to demonstrate that cartilage nanoindentation modulus is a highly sensitive indicator of the onset and spatiotemporal progression of post-traumatic osteoarthritis (PTOA) in murine models. DESIGN: Destabilization of the medial meniscus (DMM) surgery was performed on the right knees of 12-week old male, wild-type C57BL/6 mice, with Sham control on contralateral left knees. Atomic force microscopy (AFM)-based nanoindentation was applied to quantify the nanoindentation modulus, Eind, of femoral condyle cartilage at 3 days to 12 weeks after surgery. The modulus changes were compared against the timeline of histological OA signs. Meanwhile, at 8 weeks after surgery, changes in meniscus, synovium and subchondral bone were evaluated to reveal the spatial progression of PTOA. RESULTS: The modulus of medial condyle cartilage was significantly reduced at 1 week after DMM, preceding the histological OA signs, which only became detectable at 4-8 weeks after. This reduction is likely due to concomitantly elevated proteolytic activities, as blocking enzymatic activities in mice can attenuate this modulus reduction. In later OA, lateral condyle cartilage and medial meniscus also started to be weakened, illustrating the whole-organ nature of PTOA. CONCLUSIONS: This study underscores the high sensitivity of nanoindentation in examining the initiation, attenuation and progression of PTOA in murine models. Meanwhile, modulus changes highlight concomitant changes in lateral cartilage and meniscus during the advancement of OA.

Preparation of a Three-Dimensional Reduced Graphene Oxide Film by Using the Langmuir-Blodgett Method.

The Langmuir-Blodgett method has always been traditionally utilized in the deposition of two-dimensional structures. In this work, however, we employed the method to deposit three-dimensional reduced graphene oxide layers using an unconventional protocol for the first time. This was achieved by carrying out the dipping process after the collapse pressure or breaking point, which results in the formation of a highly porous three-dimensional surface topography. By varying the number of deposition layers, the porosity could be optimized from nanometer to micrometer dimensions. Employed as bioelectrodes, these three-dimensional reduced graphene oxide layers may allow improved adhesion and biocompatibility compared to the conventional two-dimensional surfaces. A larger number of pores also improves the mass transport of materials and therefore increases the charge-sustaining capacity and sensitivity. This could ultimately improve the performance of biofuel cells and other electrode-based systems.

National patterns of Escherichia coli O157 infections, USA, 1996-2011.

US public health laboratories began reporting Escherichia coli O157 isolates to CDC in 1996. We describe temporal and geographical patterns of isolates reported from 1996 to 2011 and demographics of persons whose specimens yielded isolates. We calculated annual E. coli O157 isolation rates/100 000 persons by patient's state of residence, county of residence, age, and sex using census data. The average annual isolation rate was 0·84. The average isolation rate in northern states (1·52) was higher than in southern states (0·43). Counties with ⩾76% rural population had a lower isolation rate (0·67) than counties with ⩽25%, 26-50%, and 51-75% rural populations (0·81, 0·92, and 0·81, respectively). The highest isolation rate (3·19) was in children aged 1-4 years. Infections were seasonal with 49% of isolates collected during July to September. Research into reasons for higher incidence in northern states and for seasonality could guide strategies to prevent illnesses.

Discontinuation of leisure time impact-loading exercise is related to reduction of a calcaneus quantitative ultrasound parameter in young adult Japanese females: a 3-year follow-up study.

UNLABELLED: A 3-year follow-up study on 334 young Japanese females enrolled in a university at the age of 18 years revealed that discontinuation of leisure time impact-loading exercises performed in junior high and/or high school was associated with increased risk of reduction in calcaneus osteo-sono assessment index (OSI). INTRODUCTION: Bone strength rapidly increases during puberty and reaches its peak by the end of adolescence. The aim of this study was to determine the lifestyle factors that influence the maintenance of calcaneus OSI in young adult females around the time when peak bone mass is attained. METHODS: Annual health checkups including OSI measurements, anthropometrics, lifestyle analysis, and blood examination were performed 4 times on 334 Japanese females enrolled in a university at the age of 18 years. According to the slope of OSI change during the 3-year follow-up, the subjects were grouped into two categories: OSI loss (the lowest tertile) and OSI gain/stable (the second and third tertiles). RESULTS: At the baseline assessment, the OSI loss group had higher OSI and height and an earlier menarche age than the OSI gain/stable group. Performing leisure time impact-loading exercise in junior high and/or high school but discontinuing it at university was associated with increased risk of OSI loss, independent of OSI, height and weight at the age of 18 years, weight change during follow-up, age of menarche, energy-adjusted nutrient intake, and alcohol drinking; the odds ratios were 4.1-4.9 compared with those performing impact-loading exercise at university. In particular, duration, frequency, and subjective intensity of impact-loading exercise during high school were positively associated with OSI loss. CONCLUSION: Discontinuation of leisure time impact-loading exercises performed during late adolescence is associated with an increased risk of OSI loss in young adult females during the 3-year follow-up period.

Pre-existing medical conditions associated with Vibrio vulnificus septicaemia.

Vibrio vulnificus (Vv) can result in severe disease. Although pre-existing liver disease is a recognized risk factor for serious infection, the relative importance of other comorbidities has not been fully assessed. We analysed reports of Vv infections submitted to CDC from January 1988 to September 2006 in order to assess the role of pre-existing conditions contributing to severe outcomes. A total of 1212 patients with Vv infection were reported. Only patients with liver disease [adjusted odds ratio (aOR) 5.1)] were more likely to become septic when exposure was due to contaminated food. Patients with liver disease (aOR 4.1), a haematological disease (aOR 3.2), or malignancy (aOR 3.2) were more likely to become septic when infection was acquired via a non-foodborne exposure. As such, patients with these pre-existing medical conditions should be advised of the risk of life-threatening illness after eating undercooked contaminated seafood or exposing broken skin to warm seawater.

Concurrent detection of other respiratory viruses in children shedding viable human respiratory syncytial virus.

Human respiratory syncytial virus (HRSV) is an important cause of respiratory disease. The majority of studies addressing the importance of virus co-infections to the HRSV-disease have been based on the detection of HRSV by RT-PCR, which may not distinguish current replication from prolonged shedding of remnant RNA from previous HRSV infections. To assess whether co-detections of other common respiratory viruses are associated with increased severity of HRSV illnesses from patients who were shedding viable-HRSV, nasopharyngeal aspirates from children younger than 5 years who sought medical care for respiratory infections in Ribeirão Preto (Brazil) were tested for HRSV by immunofluorescence, RT-PCR and virus isolation in cell culture. All samples with viable-HRSV were tested further by PCR for other respiratory viruses. HRSV-disease severity was assessed by a clinical score scale. A total of 266 samples from 247 children were collected and 111 (42%) were HRSV-positive. HRSV was isolated from 70 (63%), and 52 (74%) of them were positive for at least one additional virus. HRSV-positive diseases were more severe than HRSV-negative ones, but there was no difference in disease severity between patients with viable-HRSV and those HRSV-positives by RT-PCR. Co-detection of other viruses did not correlate with increased disease severity. HRSV isolation in cell culture does not seem to be superior to RT-PCR to distinguish infections associated with HRSV replication in studies of clinical impact of HRSV. A high rate of co-detection of other respiratory viruses was found in samples with viable-HRSV, but this was not associated with more severe HRSV infection.

High-power laser experiment on developing supercritical shock propagating in homogeneously magnetized plasma of ambient gas origin.

A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.

Electrophoretic fabrication of chitosan-zirconium-oxide nanobiocomposite platform for nucleic acid detection.

The present work describes electrophoretic fabrication of nanostructured chitosan-zirconium-oxide composite (CHIT-NanoZrO(2)) film (180 nm) onto indium-tin-oxide (ITO)-coated glass plate. This nanobiocomposite film has been explored as immobilization platform for probe DNA specific to M. Tuberculosis as model biomolecule to investigate its sensing characteristics. It is revealed that pH-responsive behavior of CHIT and its cationic skeleton is responsible for the movement of CHIT-NanoZrO(2) colloids toward cathode during electrophoretic deposition. The FT-IR, SEM, TEM, and EDX techniques have been employed for the structural, morphological, and composition analysis of the fabricated electrodes. The morphological studies clearly reveal uniform inter-linking and dispersion of hexagonal nanograins of ZrO(2) (30-50 nm) into the chitosan matrix, resulting in homogeneous nanobiocomposite formation. Electrochemical response measurements of DNA/CHIT-NanoZrO(2)/ITO bioelectrode, carried out using cyclic voltammetry and differential pulse voltammetry, reveal that this bioelectrode can specifically detect complementary target DNA up to 0.00078 µM with sensitivity of 6.38 × 10(-6) AµM(-1).

Multistate outbreak of Escherichia coli O157:H7 infections associated with a national fast-food chain, 2006: a study incorporating epidemiological and food source traceback results.

A multistate outbreak of Escherichia coli O157:H7 infections occurred in the USA in November-December 2006 in patrons of restaurant chain A. We identified 77 cases with chain A exposure in four states - Delaware, New Jersey, New York, and Pennsylvania. Fifty-one (66%) patients were hospitalized, and seven (9%) developed haemolytic uraemic syndrome; none died. In a matched analysis controlling for age in 31 cases and 55 controls, illness was associated with consumption of shredded iceberg lettuce [matched odds ratio (mOR) 8·0, 95% confidence interval (CI) 1·1-348·1] and shredded cheddar cheese (mOR 6·2, CI 1·7-33·7). Lettuce, an uncooked ingredient, was more commonly consumed (97% of patients) than cheddar cheese (84%) and a single source supplied all affected restaurants. A single source of cheese could not explain the regional distribution of outbreak cases. The outbreak highlights challenges in conducting rapid multistate investigations and the importance of incorporating epidemiological study results with other investigative findings.

Consequence of aging at Au/HTM/perovskite interface in triple cation 3D and 2D/3D hybrid perovskite solar cells.

Perovskite solar cells (PSCs) expressed great potentials for offering a feasible alternative to conventional photovoltaic technologies. 2D/3D hybrid PSCs, where a 2D capping layer is used over the 3D film to avoid the instability issues associated with perovskite film, have been reported with improved stabilities and high power conversion efficiencies (PCE). However, the profound analysis of the PSCs with prolonged operational lifetime still needs to be described further. Heading towards efficient and long-life PSCs, in-depth insight into the complicated degradation processes and charge dynamics occurring at PSCs' interfaces is vital. In particular, the Au/HTM/perovskite interface got a substantial consideration due to the quest for better charge transfer; and this interface is debatably the trickiest to explain and analyze. In this study, multiple characterization techniques were put together to understand thoroughly the processes that occur at the Au/HTM/perovskite interface. Inquest analysis using current-voltage (I-V), electric field induced second harmonic generation (EFISHG), and impedance spectroscopy (IS) was performed. These techniques showed that the degradation at the Au/HTM/perovskite interface significantly contribute to the increase of charge accumulation and change in impedance value of the PSCs, hence resulting in efficiency fading. The 3D and 2D/3D hybrid cells, with PCEs of 18.87% and 20.21%, respectively, were used in this study, and the analysis was performed over the aging time of 5000 h. Our findings propose that the Au/HTM/perovskite interface engineering is exclusively essential for attaining a reliable performance of the PSCs and provides a new perspective towards the stability enhancement for the perovskite-based future emerging photovoltaic technology.

Prevention of systemic lupus erythematosus in autoimmune BXSB mice by a transgene encoding I-E alpha chain.

Males from the BXSB murine strain (H-2b) spontaneously develop an autoimmune syndrome with features of systemic lupus erythematosus (SLE), which results in part from the action of a mutant gene (Yaa) located on the Y chromosome. Like other H-2b mice, the BXSB strain does not express the class II major histocompatibility complex antigen, I-E. Here we report that the expression of I-E (E alpha dE beta b) in BXSB males bearing an E alpha d transgene prevents hypergammaglobulinemia, autoantibody production, and subsequent autoimmune glomerulonephritis. These transgenic mice bear on the majority of their B cells not only I-E molecules, but also an I-E alpha chain-derived peptide presented by a higher number of I-Ab molecules, as recognized by the Y-Ae monoclonal antibody. The I-E+ B cells appear less activated in vivo than the I-E- B cells, a minor population. This limited activation of the I-E+ B cells does not reflect a functional deficiency of this cell population, since it can be stimulated to IgM production in vitro by lipopolysaccharides at an even higher level than the I-E- B cell population. The development of the autoimmune syndrome in the transgenic and nontransgenic bone marrow chimeric mice argues against the possibility that the induction of regulatory T cells or clonal deletion of potential autoreactive T cells as a result of I-E expression is a mechanism of the protection conferred by the E alpha d transgene. We propose a novel mechanism by which the E alpha d transgene protects BXSB mice against SLE: overexpression of I-E alpha chains results in the generation of excessive amounts of a peptide displaying a high affinity to the I-Ab molecule, thereby competing with pathogenic autoantigen-derived peptides for presentation by B lymphocytes and preventing their excessive stimulation.

Characterization of the 4C8 antigen involved in transendothelial migration of CD26(hi) T cells after tight adhesion to human umbilical vein endothelial cell monolayers.

In extravasation of T cells, little is known about the mechanisms of transendothelial migration subsequent to the T cells' tight adhesion to endothelium. To investigate these mechanisms, we developed a monoclonal antibody (mAb), termed anti-4C8, that blocks transmigration but not adhesion in a culture system in which high CD26-expressing (CD26(hi)) T cells preferentially migrate through human umbilical vein endothelial cell (HUVEC) monolayers cultured on collagen gels. Anti-4C8 reacted with all CD3(+) T cells and monocytes but not neutrophils or HUVECs. The structure defined by this antibody was an 80-kD molecule. The mAb at 1 mug/ml inhibited 80-90% of migration of CD3(+) T cells through unstimulated and interferon gamma-stimulated HUVEC monolayers without interfering with adhesion and cell motility. When added to the cultures after the adhesion, anti-4C8 completely blocked subsequent transmigration of adherent T cells. Phase-contrast and electron microscopy revealed that T cells are arrested at the intercellular junctions of HUVECs in the presence of anti-4C8. Anti-4C8 exhibited agonistic effects on resting T cells without other stimuli under culture conditions in which anti-4C8 can stimulate T cells. First, in the checkerboard assay using collagen gels, the antibody promoted chemokinetic migration of the cells in a dose-dependent manner from 0.1 to 10 mug/ml. The predominant population of T cells that migrated into collagen gels with impregnated anti-4C8 were CD26(hi). Second, solid-phase-immobilized anti-4C8 induced adhesion of T cells to the substrate, often with polarizations in cell shape and large pseudopods rich in filamentous (F-) actin. Third, soluble anti-4C8 augmented F-actin content preferentially in CD26(hi) T cells when added to T cells at a high dose of 10 mug/ml. Finally, both anti-4C8-induced chemokinetic migration and transendothelial migration were inhibited by pretreatment of T cells with pertussis toxin. These findings suggest that stimulation via the 4C8 antigen increases cell motility of CD26(hi) cells with profound cytoskeletal changes through signaling pathways including G proteins. The 4C8 antigen may be involved in preferential transmigration of CD26(hi) cells adherent to HUVECs.

ACO1, a gene for aminocyclopropane-1-carboxylate oxidase: effects on internode elongation at the heading stage in rice.

Although reports on a gene for 1-amino-cyclopropane-1-carboxylate (ACC) oxidase (ACO1) in rice (Oryza sativa L.) suggest that high levels of its transcript are associated with internode elongation of deep-water rice during submergence, the role of ACO1 in rice development is largely unknown. The tissue-specificity of ACO1 expression indicated that its transcript significantly accumulated in lower parts of elongating internodes at the heading stage. Histochemical analysis and in situ hybridization showed that the ACO1 expression was localized in the basal parts of leaf sheaths immediately above nodes or the lower parts of elongating internodes. To further examine the role of ACO1, ACO1-deficient (aco1) and overexpressing (ACO1-OX) mutants were characterized. The total length of the elongated internodes of aco1 mutants was slightly shorter than that of wild-type plants and that of ACO1-OX mutants was longer. Interestingly, expression of the ACC synthase gene ACS1 and ethylene signalling gene OsEIN2 was up-regulated in the aco1 mutants. This study suggests that the ACO1 has a little effect on internode elongation at the heading stage, and that up-regulation of the ACS1 and OsEIN2 expression may attenuate inhibition of internode elongation.

Pregnancy-associated listeriosis.

Infection by Listeria monocytogenes in pregnant women may result in fetal loss or invasive disease in the newborn. We examined listeriosis cases reported through the U.S. Listeria Initiative during 2004-2007. Cases were classified as pregnancy-associated if illness occurred in a pregnant woman or an infant aged <28 days. Of 758 reported Listeria cases, 128 (16.9%) were pregnancy-associated. Maternal infection resulted in four neonatal deaths and 26 (20.3%) fetal losses. Invasive illnesses in newborns (n=85) were meningitis (32.9%) and sepsis (36.5%). Pregnant women with Listeria were more likely to report Hispanic ethnicity (52.8% vs. 25.6%, respectively; OR 3.3 95% CI 2.2-4.8) than mothers giving live birth in the USA during 2005 and were more likely to report consumption of Mexican-style cheese (OR 2.6, 95% CI 1.6-4.2) than were non-pregnant patients with Listeria infection. Pregnant woman comprised a considerable proportion of reported listeriosis cases. Further declines in pregnancy-associated listeriosis will require education about avoiding high-risk foods, and continued regulatory and industry efforts to decrease Listeria in foods.

Susceptibility of patients receiving chemotherapy for haematological malignancies to scabies.

BACKGROUND: Scabies is a contagious dermatosis. The risk factors for its transmission remain unclear. A scabies outbreak, involving patients who were receiving chemotherapy for haematological malignancies, occurred at our hospital. METHODS: The outbreak population was analysed to determine whether the incidence of scabies was higher among contact patients receiving chemotherapy for haematological malignancies. RESULTS: A patient with crusted scabies was the index case, and 18 of 78 contact healthcare workers (HCWs) and 22 of 135 contact patients were diagnosed with classical scabies. Ten of 17 contact patients with haematological malignancies and 12 of 118 contact patients with other diseases were infected with scabies. The incidence rate was significantly higher among the patients with haematological malignancies (P<0.001). The patients with haematological malignancies had a significantly lower mean minimum neutrophil count than those with other diseases (1159/µL vs 3761/µL, P=0.0012). Most haematological patients did not require special nursing assistance, suggesting that the higher incidence of scabies among these patients resulted from their immunodeficiency rather than greater skin-to-skin contact with infected HCWs. CONCLUSION: Our study suggests that patients receiving chemotherapy for haematological malignancies are more susceptible to scabies than patients with other diseases, and require stricter protection.

Effect of vanadate on cartilage-matrix proteoglycan synthesis in rabbit costal chondrocyte cultures.

The effect of vanadate on proteoglycan synthesis by cultured rabbit costal chondrocytes was examined. Rabbit chondrocytes were seeded at low densities and grown to confluency in medium supplemented with 10% fetal bovine serum, and then the serum concentration was reduced to 0.3%. At the low serum concentration, chondrocytes adopted a fibroblastic morphology. Addition of 4 microM vanadate to the culture medium induced a morphologic differentiation of the fibroblastic cells to spherical chondrocytes, and increased by two- to threefold incorporation of [35S]sulfate and [3H]glucosamine into large, chondroitin sulfate proteoglycans. The stimulation of incorporation of labeled precursors reflected real increases in proteoglycan synthesis, in that chemical analyses showed increases in the accumulation of macromolecules containing hexuronic acid and hexosamine in vanadate-maintained cultures. However, vanadate had only a marginal effect on [35S]sulfate incorporation into small proteoglycans and [3H]glucosamine incorporation into hyaluronic acid and chondroitinase AC-resistant material. These results provide evidence that vanadate selectively stimulates the synthesis of proteoglycans characteristically found in cartilage by rabbit costal chondrocyte cultures.

Transcription factor ERG variants and functional diversification of chondrocytes during limb long bone development.

During limb development, chondrocytes located at the epiphyseal tip of long bone models give rise to articular tissue, whereas the more numerous chondrocytes in the shaft undergo maturation, hypertrophy, and mineralization and are replaced by bone cells. It is not understood how chondrocytes follow these alternative pathways to distinct fates and functions. In this study we describe the cloning of C-1-1, a novel variant of the ets transcription factor ch-ERG. C-1-1 lacks a short 27-amino acid segment located approximately 80 amino acids upstream of the ets DNA binding domain. We found that in chick embryo long bone anlagen, C-1-1 expression characterizes developing articular chondrocytes, whereas ch-ERG expression is particularly prominent in prehypertrophic chondrocytes in the growth plate. To analyze the function of C-1-1 and ch-ERG, viral vectors were used to constitutively express each factor in developing chick leg buds and cultured chondrocytes. We found that virally driven expression of C-1-1 maintained chondrocytes in a stable and immature phenotype, blocked their maturation into hypertrophic cells, and prevented the replacement of cartilage with bone. It also induced synthesis of tenascin-C, an extracellular matrix protein that is a unique product of developing articular chondrocytes. In contrast, virally driven expression of ch-ERG significantly stimulated chondrocyte maturation in culture, as indicated by increases in alkaline phosphatase activity and deposition of a mineralized matrix; however, it had modest effects in vivo. The data show that C-1-1 and ch-ERG have diverse biological properties and distinct expression patterns during skeletogenesis, and are part of molecular mechanisms by which limb chondrocytes follow alternative developmental pathways. C-1-1 is the first transcription factor identified to date that appears to be instrumental in the genesis and function of epiphyseal articular chondrocytes.