Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated T-cells 5 in vitro

Abstract Introduction: Chondrocytes experience a hypertonic environment compared to plasma (280 mOsm) due to the high fixed negative charge density of cartilage. Standard isolation of chondrocytes removes their hypertonic matrix, exposing them to non-physiological conditions. During in-vitro expansion, chondrocytes quickly lose their specialized phenotype, making them inappropriate for cell-based regenerative strategies. We aimed to elucidate the effects of tonicity during isolation and in-vitro expansion on chondrocyte phenotype. Methods: Human articular chondrocytes were isolated and subsequently expanded at control tonicity (280 mOsm) or at moderately elevated, physiological, tonicity (380 mOsm). The effects of physiological tonicity on chondrocyte proliferation and chondrogenic marker expression were evaluated. The role of Tonicity-responsive Enhancer Binding Protein (TonEBP/NFAT5) in response to physiological tonicity was investigated using nuclear factor of activated T-cells 5 (NFAT5) RNA interference. Results: Moderately elevated, physiological, tonicity (380 mOsm) did not affect chondrocyte proliferation, while higher tonicities inhibited proliferation and diminished cell viability. Physiological tonicity improved expression of chondrogenic markers and NFAT5 and its target genes, while suppressing dedifferentiation marker collagen type I and improving type II/type I expression ratios >100-fold. Effects of physiological tonicity were similar in osteoarthritic and ‘normal’ (non-osteoarthritic) chondrocytes, indicating a disease-independent mechanism. NFAT5 RNA interference abolished tonicity-mediated effects and revealed that NFAT5 positively regulates collagen type II expression, while suppressing type I. Conclusions: Physiological tonicity provides a simple, yet effective, means to improve phenotypical characteristics during cytokine-free isolation and in-vitro expansion of human articular chondrocytes. Our findings will lead to the development of improved cell-based repair strategies for chondral lesions and provides important insights into mechanisms underlying osteoarthritic progression

Patients with low back pain differ from those who also have leg pain or signs of nerve root involvement - A cross-sectional study

Background: Leg pain associated with low back pain (LBP) is recognized as a risk factor for a poor prognosis, and is included as a component in most LBP classification systems. The location of leg pain relative to the knee and the presence of a positive straight leg raise test have been suggested to have clinical implications. To understand differences between such leg pain subgroups, and whether differences include potentially modifiable characteristics, the purpose of this paper was to describe characteristics of patients classified into the Quebec Task Force (QTF) subgroups of: 1) LBP only, 2) LBP and pain above the knee, 3) LBP and pain below the knee, and 4) LBP and signs of nerve root involvement. Methods. Analysis of routine clinical data from an outpatient department. Based on patient reported data and clinical findings, patients were allocated to the QTF subgroups and described according to the domains of pain, activity limitation, work participation, psychology, general health and clinical examination findings. Results: A total of 2,673 patients aged 18-95 years (median 47) who were referred for assessment of LBP were included. Increasing severity was consistently observed across the subgroups from LBP only to LBP with signs of nerve root involvement although subgroup differences were small. LBP patients with leg pain differed from those with LBP only on a wide variety of parameters, and patients with signs of nerve root involvement had a more severe profile on almost all measures compared with other patients with back-related leg pain. Conclusion: LBP patients with pain referral to the legs were more severely affected than those with local LBP, and patients with signs of nerve root involvement were the ones most severily affected. These findings underpin the concurrent validity of the Quebec Task Force Classification. However, the small size of many between-subgroup differences amid the large variability in this sample of cross-sectional data also underlines that the heterogeneity of patients with LBP is more complex than that which can be explained by leg pain patterns alone. The implications of the observed differences also require investigation in longitudinal studies

The methodological quality of systematic reviews comparing temporomandibular joint disorder surgical and non-surgical treatment

<p>Abstract</p> <p>Background</p> <p>Temporomandibular joint disorders (TMJD) are multifactor, complex clinical problems affecting approximately 60–70% of the general population, with considerable controversy about the most effective treatment. For example, reports claim success rates of 70% and 83% for non-surgical and surgical treatment, whereas other reports claim success rates of 40% to 70% for self-improvement without treatment. Therefore, the purpose of this study was to (1) identify systematic reviews comparing temporomandibular joint disorder surgical and non-surgical treatment, (2) evaluate their methodological quality, and (3) evaluate the evidence grade within the systematic reviews.</p> <p>Methods</p> <p>A search strategy was developed and implemented for MEDLINE, Cochrane Library, LILACS, and Brazilian Dentistry Bibliography databases. Inclusion criteria were: systematic reviews (± meta-analysis) comparing surgical and non-surgical TMJD treatment, published in English, Spanish, Portuguese, Italian, or German between the years 1966 and 2007(up to July). Exclusion criteria were: <it>in vitro </it>or animal studies; narrative reviews or editorials or editorial letters; and articles published in other languages. Two investigators independently selected and evaluated systematic reviews. Three different instruments (AMSTAR, OQAQ and CASP) were used to evaluate methodological quality, and the results averaged. The GRADE instrument was used to evaluate the evidence grade within the reviews.</p> <p>Results</p> <p>The search strategy identified 211 reports; of which 2 were systematic reviews meeting inclusion criteria. The first review met 23.5 ± 6.0% and the second met 77.5 ± 12.8% of the methodological quality criteria (mean ± sd). In these systematic reviews between 9 and 15% of the trials were graded as high quality, and 2 and 8% of the total number of patients were involved in these studies.</p> <p>Conclusion</p> <p>The results indicate that in spite of the widespread impact of TMJD, and the multitude of potential interventions, clinicians have expended sparse attention to systematically implementing clinical trial methodology that would improve validity and reliability of outcome measures. With some 20 years of knowledge of evidence-based healthcare, the meager attention to these issues begins to raise ethical issues about TMJD trial conduct and clinical care.</p

Autonomic and muscular responses and recovery to one-hour laboratory mental stress in healthy subjects

<p>Abstract</p> <p>Background</p> <p>Stress is a risk factor for musculoskeletal pain. We wanted to explore stress related physiology in healthy subjects in order to gain insight into mechanisms of pain development which may relate to the pathophysiology of musculoskeletal pain disorders.</p> <p>Methods</p> <p>Continuous blood pressure, heart rate, finger skin blood flow, respiration, surface electromyography together with perception of pain, fatigue and tension were recorded on 35 healthy women and 9 healthy men before, during a 60 minute period with task-related low-grade mental stress, and in the following 30 minute rest period.</p> <p>Results</p> <p>Subjects responded physiologically to the stressful task with an increase in trapezius and frontalis muscle activity, increased blood pressure, respiration frequency and heart rate together with reduced finger skin blood flow. The blood pressure response and the finger skin blood flow response did not recover to baseline values during the 30-minute rest period, whereas respiration frequency, heart rate, and surface electromyography of the trapezius and frontalis muscles recovered to baseline within 10 minutes after the stressful task. Sixty-eight percent responded subjectively with pain development and 64% reported at least 30% increase in pain. Reduced recovery of the blood pressure was weakly correlated to fatigue development during stress, but was not correlated to pain or tension.</p> <p>Conclusion</p> <p>Based on a lack of recovery of the blood pressure and the acral finger skin blood flow response to mental stress we conclude that these responses are more protracted than other physiological stress responses.</p

Back Complaints in the Elders (BACE); design of cohort studies in primary care: an international consortium

Background: Although back complaints are common among older people, limited information is available in the literature about the clinical course of back pain in older people and the identification of older persons at risk for the transition from acute back complaints to chronic back pain. The aim of this study is to assess the course of back complaints and identify prognostic factors for the transition from acute back complaints to chronic back complaints in older people who visit a primary health care physician. Methods/design. The design is a prospective cohort study with one-year follow-up. There will be no interference with usual care. Patients older than 55 years who consult a primary health care physician with a new episode of back complaints will be included in this study. Data will be collected using a questionnaire, physical examination and X-ray at baseline, and follow-up questionnaires afte