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Subjects with developmental dysplasia of the hip (DDH) often show early-onset osteoarthritis (OA); however, the molecular mechanisms underlying this pathology are not known. We investigated whether cellular changes in chondrocytes from OA cartilage can be detected in chondrocytes from DDH cartilage before histological manifestations of degeneration. We characterized undamaged and damaged articular cartilage from 22 participants having hip replacement surgery with and without DDH (9 DDH-OA, 12 OA-only, one femoral fracture). Tissue immunostaining revealed changes in damaged OA-only cartilage that was also found in undamaged DDH-OA cartilage. Chondrocytes in situ from both groups show: (i) thicker fibers of vimentin intermediate filaments, (ii) clusters of integrin α 5 β 1 , (iii) positive MMP13 staining and (iv) a higher percentage of cells expressing the serine protease HtrA1. Further characterization of the extracellular matrix showed strong aggrecan and collagen II immunostaining in undamaged DDH cartilage, with no evidence of augmented cell death by activation of caspase 3. These findings suggest that early events in DDH cartilage originate at the chondrocyte level and that DDH cartilage may provide a novel opportunity to study these early changes for the development of therapeutic targets for OA.

Osteonecrosis (ON) of the femoral head (ONFH) is a devastating bone disease affecting over 20 million people worldwide. ONFH is caused by a disruption of the blood supply, leading to necrotic cell death and increased inflammation. Macrophages are the key cells mediating the inflammatory responses in ON. It is unclear what the dynamic phenotypes of macrophages are and what mechanisms may affect macrophage polarization and, therefore, the healing process. In our preliminary study, we found that there is an invasion of macrophages into the repair tissue during ON healing. Interestingly, in both ONFH patients and a mouse ON model, fat was co-labeled within macrophages using immunofluorescence staining, indicating the phagocytosis of fat by macrophages. To study the effects of fat phagocytosis on the macrophage phenotype, we set up an in vitro macrophage and fat co-culture system. We found that fat phagocytosis significantly decreased M1 marker expression, such as IL1β and iNOS, in macrophages, whereas the expression of the M2 marker Arg1 was significantly increased with fat phagocytosis. To investigate whether the polarization change is indeed mediated by phagocytosis, we treated the cells with Latrunculin A (LA, which inhibits actin polymerization and phagocytosis). LA supplementation significantly reversed the polarization marker gene changes induced by fat phagocytosis. To provide an unbiased transcriptional gene analysis, we submitted the RNA for bulk RNA sequencing. Differential gene expression (DGE) analysis revealed that the top upregulated genes were related to anti-inflammatory responses, while proinflammatory genes were significantly downregulated. Additionally, using pathway enrichment and network analyses (Metascape), we confirmed that gene-enriched categories related to proinflammatory responses were significantly downregulated in macrophages with fat phagocytosis. Finally, we validated the similar macrophage phenotype changes in vivo. To summarize, we discovered that fat phagocytosis occurs in both ONFH patients and an ON mouse model, which inhibits proinflammatory responses with increased anabolic gene expression in macrophages. This fat-phagocytosis-induced macrophage phenotype is consistent with the in vivo changes shown in the ON mouse model. Our study reveals a novel phagocytosis-mediated macrophage polarization mechanism in ON, which fills in our knowledge gaps of macrophage functions and provides new concepts in macrophage immunomodulation as a promising treatment for ON.

Mechanical loading of the intervertebral disc (IVD) initiates cell‐mediated remodeling events that contribute to disc degeneration. Cells of the IVD, nucleus pulposus (NP) and anulus fibrosus (AF), will exhibit various responses to different mechanical stimuli which appear to be highly dependent on loading type, magnitude, duration, and anatomic zone of cell origin. Cells of the NP, the innermost region of the disc, exhibit an anabolic response to low‐moderate magnitudes of static compression, osmotic pressure, or hydrostatic pressure, while higher magnitudes promote a catabolic response marked by increased protease expression and activity. Cells of the outer AF are responsive to physical forces in a manner that depends on frequency and magnitude, as are cells of the NP, though they experience different forces, deformations, pressure, and osmotic pressure in vivo. Much remains to be understood of the mechanotransduction pathways that regulate IVD cell responses to loading, including responses to specific stimuli and also differences among cell types. There is evidence that cytoskeletal remodeling and receptor‐mediated signaling are important mechanotransduction events that can regulate downstream effects like gene expression and posttranslational biosynthesis, all of which may influence phenotype and bioactivity. These and other mechanotransduction events will be regulated by known and to‐be‐discovered cell‐matrix and cell‐cell interactions, and depend on composition of extracellular matrix ligands for cell interaction, matrix stiffness, and the phenotype of the cells themselves. Here, we present a review of the current knowledge of the role of mechanical stimuli and the impact upon the cellular response to loading and changes that occur with aging and degeneration of the IVD. Substructures of the intervertebral disc (IVD) include the anulus fibrosus (AF), cartilage endplate (CEP) and nucleus pulposus (NP) drawn as shown. These structures experience a wide range of physical stimuli that generate cellular responses through cytoskeletal remodeling, and cell‐matrix and cell‐cell interactions, that can drive changes to extracellular matrix (ECM). Altered magnitudes of physical stimuli with disc degeneration can drive degenerative changes.

Interferons (IFNs) are a family of cytokines that activate the JAK-STAT signaling pathway to induce an antiviral state in cells. Interleukin 27 (IL-27) is a member of the IL-6 and/or IL-12 family that elicits both pro- and anti-inflammatory responses. Recent studies have reported that IL-27 also induces a robust antiviral response against diverse viruses, both in vitro and in vivo , suggesting that IFNs and IL-27 share many similarities at the functional level. However, it is still unknown how similar or different IFN- and IL-27-dependent signaling pathways are. To address this question, we conducted a comparative analysis of the transcriptomic profiles of human monocyte-derived macrophages (MDMs) exposed to IL-27 and those exposed to recombinant human IFN-α, IFN-γ, and IFN-λ. We utilized bioinformatics approaches to identify common differentially expressed genes between the different transcriptomes. To verify the accuracy of this approach, we used RT-qPCR, ELISA, flow cytometry, and microarrays data. We found that IFNs and IL-27 induce transcriptional changes in several genes, including those involved in JAK-STAT signaling, and induce shared pro-inflammatory and antiviral pathways in MDMs, leading to the common and unique expression of inflammatory factors and IFN-stimulated genes (ISGs)Importantly, the ability of IL-27 to induce those responses is independent of IFN induction and cellular lineage. Additionally, functional analysis demonstrated that like IFNs, IL-27-mediated response reduced chikungunya and dengue viruses replication in MDMs. In summary, IL-27 exhibits properties similar to those of all three types of human IFN, including the ability to stimulate a protective antiviral response. Given this similarity, we propose that IL-27 could be classified as a distinct type of IFN, possibly categorized as IFN-pi (IFN-π), the type V IFN (IFN-V).

The short physical performance battery (SPPB) is a physical performance test of lower extremity function designed for non-disabled older adults. We aimed to establish reference values for community-dwelling Colombian adults aged 60 years or older in terms of (1) the total score; (2) the three subtest scores (walking speed, standing balance performance, and five times sit-to-stand test); and (3) the time to complete the five times sit-to-stand test, s and the walking speed test. Additionally, we sought to explore how much of the variance in the SPPB subtest scores could be explained by anthropometric variables (age, body mass, height, body mass index, and calf circumference). Participants were men and women aged 60 years or older who participated in the Health and Well-being and Aging Survey in Colombia, 2015. A sample of 4,211 participants (57.3% women) completed the SPPB test, and their anthropometric variables were evaluated. Age-specific percentiles were calculated using the LMS method (3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles). The mean SPPB total score for the entire sample was 8.73 (2.0) points. On average, the total SPPB score was 0.85 points greater in men than in women ( < 0.001). Significant sex differences were observed in all three age groups tested (60-69, 70-79, and 80+ years). In the full sample, our findings suggested that age, body mass, height, body mass index, and calf circumference are significant contributors to walking speed ( < 0.001) after controlling for confounding factors, including ethnicity, socioeconomic status, and urbanicity. Percentile values are of interest to identify target populations for primary prevention and to estimate the proportion of high or low values for SPPB measures in community-dwelling Colombians aged at least 60 years.

The interaction between cells and their extracellular matrix (ECM) is crucial to maintain both tissue and cellular homeostasis. Indeed, cell phenotype is significantly affected by the 3D microenvironment. Although highly convenient, isolating cells from the intervertebral disc (IVD) and growing them in 2D on plastic or glass substrates, causes them to rapidly lose their phenotype and consequently alter their gene and protein expression. While characterization of cells in their native or simulated 3D environment is preferred, such approaches are complexed by limitations in phenotypic readouts. In the current article, we describe a detailed protocol to study nucleus pulposus cells in 3D—embedded in alginate as a permeable cell‐staining reservoir, as well as adaptation for cell staining and imaging in their native ECM. This method allows for detection of phenotypical and cytoskeletal changes in cells within native tissue or 3D alginate beads using confocal microscopy, without the need for histological processing. In this article, we explain easy to adopt protocols that permit visualization of cells in their native matrix or biomimetic 3D system, including (A) how to build an inexpensive and easy to assemble sample holder that allows confocal visualization of cells embedded in alginate beads (B), and how to process rodent nucleus pulposus (C) for better staining and confocal visualization of cells in situ (D). Both without the need of further histological processing.

Excess central adiposity accelerates the decline of muscle strength in older people. Additionally, hyperglycemia, independent of associated comorbidities, is related to the loss of muscle mass and strength, and contributes to functional impairment in older adults. We studied the mediation effect of glucose levels, in the relationship between abdominal obesity and relative handgrip strength (HGS). A total of 1571 participants (60.0% women, mean age 69.1 ± 7.0 years) from 86 municipalities were selected following a multistage area probability sampling design. Measurements included demographic and anthropometric/adiposity markers (weight, height, body mass index, and waist circumference). HGS was measured using a digital dynamometer for three sets and the mean value was recorded. The values were normalized to body weight (relative HGS). Fasting glucose was analyzed by enzymatic colorimetric methods. Mediation analyses were performed to identify associations between the independent variable (abdominal obesity) and outcomes (relative HGS), as well as to determine whether fasting glucose levels mediated the relationship between excess adiposity and relative HGS. A total of 1239 (78.8%) had abdominal obesity. Abdominal obesity had a negative effect on fasting glucose (β = 9.04, 95%CI = 5.87 to 12.21); while fasting glucose to relative HGS was inversely related (β = −0.003, 95%CI = −0.005 to −0.001), p < 0.001. The direct effect of abdominal obesity on relative HGS was statistically significant (β = −0.069, 95%CI = −0.082 to −0.057), p < 0.001. Lastly, fasting glucose levels mediates the detrimental effect of abdominal obesity on relative HGS (indirect effect β = −0.002, 95%CI = −0.004 to −0.001), p < 0.001. Our results suggest that the glucose level could worsen the association between abdominal obesity status and lower HGS. Thus, it is plausible to consider fasting glucose levels when assessing older adults with excess adiposity and/or suspected loss of muscle mass.

Background In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab‐to‐lab variability jeopardizes the much‐needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources. Methods The most commonly applied methods for NP cell extraction, expansion, and re‐differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, cow, and human NP tissue were experimentally assessed. Expansion and re‐differentiation media and techniques were also investigated. Results Recommended protocols are provided for extraction, expansion, and re‐differentiation of NP cells from common species utilized for NP cell culture. Conclusions This international, multilab and multispecies study identified cell extraction methods for greater cell yield and fewer gene expression changes by applying species‐specific pronase usage, 60–100 U/ml collagenase for shorter durations. Recommendations for NP cell expansion, passage number, and many factors driving successful cell culture in different species are also addressed to support harmonization, rigor, and cross‐lab comparisons on NP cells worldwide. An international group of spine scientists collaborated to standardize extraction and expansion techniques for nucleus pulposus cells to reduce variability, improve comparability between labs, and improve utilization of funding and resources.

Objetivo Caracterizar los roles y desafíos que enfrentan las mujeres con VIH, líderes de hogar, del Valle del Cauca, Colombia.Método Cualitativo exploratorio, basado en la Teoría Fundada. Los datos fueron recolectados a través de entrevistas en profundidad a 13 mujeres con VIH, jefas de hogar con edades entre los 19 y los 46 años que viven en las ciudades de Cali y Buenaventura.Resultados Los principales roles asumidos por las mujeres son el cuidado de sus hijos, el sostenimiento del hogar, las expresiones de afecto, el apoyo frente a diferentes situaciones de la vida y los procedimientos administrativos relacionados con el acceso a los servicios de salud. Entre los desafíos se mencionan aquellos aspectos relacionados con la crianza, ser modelo de autocuidado, acompañar y liderar el diagnóstico y la adherencia al tratamiento de quienes tienen menores VIH positivos, la revelación del diagnóstico, proveer las mejores condiciones de vida, y el proveer acceso a bienes y servicios.Conclusiones Los resultados del estudio resaltan los desafíos y roles que enfrentan las mujeres al vivir con una enfermedad crónica y que aún sigue estando cargados de estigma y discriminación. Se evidencian los aspectos sociales, económicos, culturales y en salud relacionados con las inequidades y desigualdades en salud, asociadas al género y al acceso a los servicios en salud, al trabajo decente y educación.

Objetivo Describir la adherencia a aspectos no-farmacológicos del tratamiento en personas con VIH/Sida de la ciudad de Cali, Colombia y establecer su relación con aspectos socio-demográficos.Material y Métodos Estudio observacional transversal, con una muestra de 277 personas con VIH/Sida de nueve instituciones de salud. Se utilizó el cuestionario de adherencia al tratamiento para el VIH/Sida.Resultados Sólo el 37 % de las personas son adherentes al tratamiento no-farmacológico. El análisis de los factores socio-demográficos relacionados con la adherencia, muestra que tienen menor oportunidad de estar adheridos los menores de 40 años.Conclusiones La adherencia al tratamiento no-farmacológica es baja y parece ser un problema generalizado en la población con VIH/Sida, si bien es más grave en menores de 40 años. Los resultados muestran que es necesario realizar intervenciones que mejoren la adherencia no-farmacológica para contribuir al control de la infección, y que éstas deben implementarse en todas las personas diagnosticadas, con especial énfasis en la población joven.