Osteoarthritis results in irreparable loss of articular cartilage. Due to its avascular nature and low mitotic activity, cartilage has little intrinsic capacity for repair. Cartilage loss leads to pain, physical disability, movement restriction, and morbidity. Various treatment strategies have been proposed for cartilage regeneration, but the optimum treatment is yet to be defined. Tissue engineering with engineered constructs aimed towards developing a suitable substrate may help in cartilage regeneration by providing the mechanical, biological and chemical support to the cells. The use of scaffold as a substrate to support the progenitor cells or autologous chondrocytes has given promising results. Leakage of cells, poor cell survival, poor cell differentiation, inadequate integration into the host tissue, incorrect distribution of cells, and dedifferentiation of the normal cartilage are the common problems in tissue engineering. Current research is focused on improving mechanical and biochemical properties of scaffold to make it more efficient. The aim of this review is to provide a critical discussion on existing challenges, scaffold type and properties, and an update on ongoing recent developments in the architecture and composition of scaffold to enhance the proliferation and viability of mesenchymal stem cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2343-2354, 2017.
Rotator cuff injury (RCI) is a major musculoskeletal disorder in the adult population where inflammation and pain are major contributing factors. Coincidence of other clinical conditions like glenohumeral arthritis aggravates inflammation and delays the healing response. The mechanism and signaling factors underlying the sustenance of inflammation in the rotator cuff joint are largely unknown. The present article aims to elucidate the involvement of inflammatory molecule, TREM-1 (Triggering Receptors Expressed on Myeloid cells-1), and danger-associated molecular patterns (DAMPs), including high mobility group protein 1 (HMGB-1) and RAGE (receptor for advanced glycation end products), in the setting of RCI with respect to the severity of glenohumeral arthritis. Biceps tendons (15 specimens) from the shoulder and blood (11 samples) from patients with glenohumeral arthritis (Group-1, n = 4) and without glenohumeral arthritis (Group-2, n = 11) after RCI surgery were obtained for the study. Molecular and morphological alterations between the groups were compared using histology, immunofluorescence, RT-PCR and flow cytometry. MRI and histomorphology assessment revealed severe inflammation in Group-1 patients while in Group-2 ECM disorganization was prominent without any hallmarks of inflammation. A significant increase in TREM-1 expression in circulating neutrophils and monocytes was observed. Elevated levels of TREM-1, HMGB-1 and RAGE in Group-1 patients along with CD68+ and CD16+ cells confirmed DAMP-mediated inflammation. Expression of TREM-1 in the tendon of Group-2 patients even in the absence of immune cells presented a new population of TREM-expressing cells that were confirmed by real-time PCR analysis and immunofluorescence. Expression of HMGB-1 and RAGE in the biceps tendon from the shoulder of patients without glenohumeral arthritis implied TREM-1-mediated inflammation without involving immune cells, whereas in patients with glenohumeral arthritis, infiltration and the activation of the immune cells, primarily macrophages, release mediators to induce inflammation. This could be the reason for ECM disorganization without the classical signs of inflammation in patients without glenohumeral arthritis.
The extracellular matrix (ECM) provides core support which is essential for the cell and tissue architectural development. The role of ECM in many pathological conditions has been well established and ECM-related abnormalities leading to serious consequences have been identified. Though much has been explored in regards to the role of ECM in soft tissue associated pathologies, very little is known about its role in inflammatory disorders in tendon. In this study, we performed microRNA (miRNA) expression analysis in the long head of the human shoulder biceps tendon to identify key genes whose expression was altered during inflammation in patients with glenohumeral arthritis. We identified differential regulation of matrix metalloproteinases (MMPs) that could be critical in collagen type replacement during tendinopathy. The miRNA profiling showed consistent results between the groups and revealed significant changes in the expression of seven different miRNAs in the inflamed tendons. Interestingly, all of these seven miRNAs were previously reported to have either a direct or indirect role in regulating the ECM organization in other pathological disorders. In addition, these miRNAs were also found to alter the expression levels of MMPs, which are the key matrix degrading enzymes associated with ECM-related abnormalities and pathologies. To our knowledge, this is the first report which identifies specific miRNAs associated with inflammation and the matrix reorganization in the tendons. Furthermore, the findings also support the potential role of these miRNAs in altering the collagen type ratio in the tendons during inflammation which is accompanied with differential expression of MMPs.
Systemic inflammation is associated with increasing age. Yet, there are limited data about the association between age and systemic inflammation within older adults, and whether older age is also associated with cellular and nuclear signaling markers of inflammation. In community-dwelling older adults (N = 262, 60–88 years), systemic levels of C-reactive protein, interleukin-6, and soluble tumor necrosis factor receptor II; levels of toll-like receptor-4–stimulated monocytic production of interleukin-6 and tumor necrosis factor α; and resting nuclear levels of activated nuclear factor kappa B and signal transducer and activator of transcription (STAT1, STAT3, STAT5) were evaluated. Adjusting for demographic and clinical factors, multivariate linear regression tested the association between age and each inflammatory marker. Age was positively associated with increased levels of interleukin-6 and soluble tumor necrosis factor receptor II (p’s < .05) and with increases in STAT1, STAT3, and STAT5 activation (p’s < .05). However, no relationship was found between age and C-reactive protein, toll-like receptor-4–stimulated interleukin-6/tumor necrosis factor alpha α production, or nuclear factor kappa B. Within a community-dwelling sample of older adults, older age is associated with increases in STAT activation, along with increases of systemic inflammatory cytokines. In older adults, heterogeneity in age-related increases in inflammatory disease risk may be related to individual variability in inflammation.
BackgroundOsteoarthritis (OA) of the knee joint is a degenerative process resulting in cartilage loss. Recent evidence suggests that OA is not merely a disease of cartilage but a disease of the entire knee joint and that inflammation may play an important role. OA has been associated with vitamin D deficiency. Vitamin D as an immunomodulator and anti-inflammatory agent may attenuate inflammation in the knee. The aim of this study was to assess the anti-inflammatory effect of vitamin D on inflammation in the knee.MethodsThis study was conducted with 13 microswine on a high cholesterol diet categorized into three groups of vitamin D-deficient, vitamin D-sufficient, and vitamin D supplementation. After 1 year, microswine were killed, and their knee joint tissues were harvested. Histological and immunofluorescence studies were carried out on the tissue specimens to evaluate the effect of vitamin D status.ResultsHistological and immunofluorescence studies of the knee joint tissues showed (1) increased inflammation in the knee joint tissues, (2) fatty infiltration in quadriceps muscle, patellar tendon, and collateral ligaments, and (3) chondrocyte clustering in the vitamin D-deficient and vitamin D-sufficient groups compared with the vitamin D supplementation group. Architectural distortion of the quadriceps muscle, patellar tendon, and collateral ligaments was also seen in the areas of inflammatory foci and fatty infiltration in the vitamin D-deficient group.ConclusionsDecreased inflammation and fatty infiltration in the vitamin D supplementation group suggest the potential role of vitamin D in attenuating inflammation and fatty infiltration as well as in protecting the architecture of the tissue in the knee joint.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1099-6) contains supplementary material, which is available to authorized users.
Spinal cord epidural stimulation (scES) has enabled volitional lower extremity movements in individuals with chronic and clinically motor complete spinal cord injury and no clinically detectable brain influence. The aim of this study was to understand whether the individuals’ neuroanatomical characteristics or positioning of the scES electrode were important factors influencing the extent of initial recovery of lower limb voluntary movements in those with clinically motor complete paralysis. We hypothesized that there would be significant correlations between the number of joints moved during attempts with scES prior to any training interventions and the amount of cervical cord atrophy above the injury, length of post-traumatic myelomalacia and the amount of volume coverage of lumbosacral enlargement by the stimulation electrode array. The clinical and imaging records of 20 individuals with chronic and clinically motor complete spinal cord injury who underwent scES implantation were reviewed and analysed using MRI and X-ray integration, image segmentation and spinal cord volumetric reconstruction techniques. All individuals that participated in the scES study (n = 20) achieved, to some extent, lower extremity voluntary movements post scES implant and prior to any locomotor, voluntary movement or cardiovascular training. The correlation results showed that neither the cross-section area of spinal cord at C3 (n = 19, r = 0.33, P = 0.16) nor the length of severe myelomalacia (n = 18, r = −0.02, P = 0.93) correlated significantly with volitional lower limb movement ability. However, there was a significant, moderate correlation (n = 20, r = 0.59, P = 0.006) between the estimated percentage of the lumbosacral enlargement coverage by the paddle electrode as well as the position of the paddle relative to the maximal lumbosacral enlargement and the conus tip (n = 20, r = 0.50, P = 0.026) with the number of joints moved volitionally. These results suggest that greater coverage of the lumbosacral enlargement by scES may improve motor recovery prior to any training, possibly because of direct modulatory effects on the spinal networks that control lower extremity movements indicating the significant role of motor control at the level of the spinal cord.
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