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ABSTRACT: Hypoxia-inducible factor 1 alpha regulates genes related to cellular survival under hypoxia. This factor is present in osteroarthritic chondrocytes, and cytokines, such as interleukin-1 beta, participate in the pathogenesis of osteoarthritis, thereby increasing the activities of proteolytic enzymes, such as matrix metalloproteinases, and accelerating cartilage destruction. We hypothesize that Hypoxia Inducible Factor-1 alpha (HIF-1α) can regulate cytokines (catabolic action) and/or growth factors (anabolic action) in osteoarthritis. The purpose of this study was to investigate the modulation of HIF-1α in human osteoarthritic chondrocytes by interleukin-1 beta (IL-1β) and insulin-like growth factors I (IGF-I) and II (IGF-II) and to determine the involvement of the phosphatidylinositol-3-kinase (PI-3K) pathway in this process.
Human osteroarthritic chondrocytes were stimulated with IL-1β, IGF-I and IGF-II and LY294002, a specific inhibitor of PI-3K. Nuclear protein levels and gene expression were analyzed by western blot and quantitative reverse transcription-polymerase chain reaction analyses, respectively.
HIF-1α expression was upregulated by IL-1β at the protein level but not at the gene level. IGF-I treatment resulted in increases in both the protein and mRNA levels of HIF-1α , whereas IGF-II had no effect on its expression. However, all of these stimuli exploited the PI-3K pathway.
IL-1β upregulated the levels of HIF-1α protein post-transcriptionally, whereas IGF-I increased HIF-1α at the transcript level. In contrast, IGF-II did not affect the protein or gene expression levels of HIF-1α . Furthermore, all of the tested stimuli exploited the PI-3K pathway to some degree. Based on these findings, we are able to suggest that Hypoxia inducible Factor-1 exhibits protective activity in chondrocytes during osteoarthritis.
Clinics (São Paulo, Brazil) 01/2012; 67(1):35-40. · 1.59 Impact Factor
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ABSTRACT: Musculoskeletal disorders are the major causes of the pain in the elderly population. Rheumatic conditions restrict participation in activities and mobility, as well as cause difficulties in the execution of self-care tasks. The assessment of health related quality of life (HRQOL) is an important indicator of the impact of rheumatic diseases on the physical, mental and social aspects. This study aims to analyze the influence of rheumatic diseases and chronic joint symptoms on the quality of life of the elderly (n=2209) aged 60 years or over. The effects of rheumatism and joint symptoms on quality of life were investigated by the Outcome Study Short-Form Health Survey (SF-36), and this analysis was adjusted for age and sex. The univariate analysis of variance and analysis of covariance (ANOVA and ANCOVAS) were used for statistical procedures, p≤0.05. Rheumatic diseases affected: functional capacity (F(1, 2012))=10.9 and pain (F(1, 2012))=34.77. Joint symptoms affected all components of the SF-36: physical functioning (F(1, 2012))=10.9; physical problems (F(1, 2012))=72.61; pain (F(1, 2012))=164.29; general health (F(1, 2012))=71.95; vitality (F(1, 2012))=55.78; social aspect (F(1, 2012))=73.14; emotional aspect (F(1, 2012))=49.09 and mental health (F(1, 2012))=44.72. There was a significant impact of rheumatic diseases on physical health, and that joint symptoms affected self-evaluations of physical and mental health. These results will contribute to a better understanding of this systemic disease and will be used for planning effective interventions.
Archives of gerontology and geriatrics 08/2011; 54(2):e77-82. · 1.36 Impact Factor
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ABSTRACT: Numerous experimental efforts have been undertaken to induce the healing of lesions within articular cartilage by re-establishing competent repair tissue. Adult mesenchymal stem cells have attracted attention as a source of cells for cartilage tissue engineering. The purpose of this study was to investigate chondrogenesis employing periosteal mesenchymal cells.
Periosteum was harvested from patients who underwent orthopedic surgeries. Mesenchymal stem cells were characterized through flow cytometry using specific antibodies. The stem cells were divided into four groups. Two groups were stimulated with transforming growth factor β3 (TGF-β3), of which one group was cultivated in a monolayer culture and the other was cultured in a micromass culture. The remaining two groups were cultivated in monolayer or micromass cultures in the absence of TGF-β3. Cell differentiation was verified through quantitative reverse transcription-polymerase chain reaction (RT-PCR) and using western blot analysis.
In the groups cultured without TGF-β3, only the cells maintained in the micromass culture expressed type II collagen. Both the monolayer and the micromass groups that were stimulated with TGF-β3 expressed type II collagen, which was observed in both quantitative RT-PCR and western blot analysis. The expression of type II collagen was significantly greater in the micromass system than in the monolayer system.
The results of this study demonstrate that the interactions between the cells in the micromass culture system can regulate the proliferation and differentiation of periosteal mesenchymal cells during chondrogenesis and that this effect is enhanced by TGF-β3.
Clinics (São Paulo, Brazil) 01/2011; 66(3):487-92. · 1.59 Impact Factor
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ABSTRACT: This study aims to determine the factors that may be related to falls in the elderly assisted by the Family Health Program (FHP). Elderly individuals aged 60 years or over, who were assisted by the FHP primary care system (n=2209), responded to a sociodemographic and health questionnaire. Mental health was evaluated using the Geriatric Depression Scale (GDS) and quality of life was assessed by the Medical Outcome Study Short-Form Health Survey (SF-36). In order to verify which independent variables affected the occurrence of falls, logistic regression analysis was performed. 27.1% of the sample reported one fall during the previous year, and 8.7% were recurrent fallers over the same period. The factors considered in the final model for falls were: age over 80 years-old, female gender, the presence of more than eight associated diseases, need for hospitalization during the previous year and appointments outside the FHP routine, hearing complaints, GDS score over 11 points, and emotional problems SF-36 score between 25 and 74 points. The factors included in the final model for falls can be easily identified and properly overcome by FHP strategy. Patient falling history investigation should thus form part of the FHP team routine. This concern should be reinforced when it comes to women aged 80 years and over.
Archives of gerontology and geriatrics 02/2010; 51(3):317-22. · 1.36 Impact Factor
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ABSTRACT: Elderly caregivers suffer physical and psychological consequences of the act of caring. The objective of this study was to characterize primary caregivers of elderly people in the community and identify the higher impacts of this activity on their life. We interviewed 127 caregivers about sociodemographic characteristics, presence of anxiety/depression (self-reporting questionnaire=SRQ), burden of care (caregiver burden scale=CBS); while their dependents were evaluated using sociodemographic questionnaires, health history, activities of daily living (ADL) scale and geriatric depression scale (GDS-15). The caregivers' mean age was 55.1+/-13.3 years; among them most were women and daughters with up to 4 years of education. The mean time as responsible for the elderly was 86.5+/-96.3 months; 56% divided the caring responsibility and 28.2% had another occupation; 32.3% presented psychoemotional illness. There was a positive correlation between the CBS and the caregiver factors: psychoemotional disorders, time as responsible for the elderly and education level; as well as between the CBS and the elderly: number of activities with dependence, presence of depression and incontinences. The correlation between the elderly's personal income and number of visits received was negative. The identification of high impacts on the caregivers' life would facilitate the professional approach.
Archives of gerontology and geriatrics 09/2009; 51(1):76-80. · 1.36 Impact Factor
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ABSTRACT: To determine whether elderly subjects with distinct histories of falls presented differences concerning the influence of sensory interaction on balance.
Cross-sectional research. Ninety-six community-dwelling elderly subjects were divided into three groups, according to the history of falls within the past year (group 1, no falls; group 2, one fall; and group 3, recurrent falls). The Clinical Test of Sensory Interaction and Balance was used to evaluate the influence of sensory inputs on standing balance. The test required the subject to maintain stability during 30 s, under six conditions: (i) firm surface with eyes open; (ii) firm surface with eyes closed; (iii) firm surface with visual conflict; (iv) unstable surface with eyes open; (v) unstable surface with eyes closed; and (vi) unstable surface with visual conflict. The time expended on conditions and the number of abnormal cases were compared between groups. Each group was evaluated in relation to its performance in the progression of conditions.
More abnormal cases occurred in group 3 compared to group 1 for conditions (iv) and (v); and compared to group 2 for condition (iv). Group 3 remained less time than group 1 under conditions (iv), (v) and (vi). Groups 1, 2 and 3 presented relevant decrements in trial duration from conditions (iv) to (v). For group 3, a significant decay was also noted from condition (i) to (ii).
Sensorial interaction in the elderly varies according to their history of falls. Thus, it is possible to correctly guide the rehabilitation process and to prevent sensorial decays according to an individual's history of falls.
Geriatrics & Gerontology International 07/2009; 9(2):165-71.
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JCR Journal of Clinical Rheumatology 11/2007; 13(5):291-2. · 1.36 Impact Factor
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ABSTRACT: The aim of this paper was to evaluate bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE), to determine the role of corticosteroids and cytotoxic drugs and to assess estrogen effect on BMD in SLE.
BMD (DEXA) at lumbar vertebrae (L2-L4) and at femoral neck was performed in 60 pre-menopausal SLE patients and in 64 controls. Estradiol level was measured in all the individuals. Age, age at disease onset, body mass index (BMI), time of disease, disease activity (SLEDAI), prednisone dose at the evaluation, total cumulative and cumulative prednisone dose in the last year and cytotoxic drugs were assessed.
The mean plasmatic estradiol was 175.9 pg/ml in patients and 149.9 in controls. BMD was inferior in patients than that in controls (P < 0.0001). The mean current, cumulative and previous year prednisone doses were, respectively, 19.17 mg/d, 28.78 g and 5.33 g. There was no association between corticosteroids or cytotoxic drug used and low bone mass. The serum concentration of estradiol did not influence the bone mass. The BMI and age at disease onset exhibited an influence on BMD at L2.
BMD was significantly lower in SLE patients but not related to CS (Corticosteroids)or other drugs; the estradiol in these patients had no effect on BMD. Low BMI interacting with early onset of disease might influence the probability of loss of bone mass.
Joint Bone Spine 02/2003; 70(1):40-5. · 2.27 Impact Factor
