Tuning the differentiation of periosteum-derived cartilage using biochemical and mechanical stimulations.

OBJECTIVE: In this study, we aim at tuning the differentiation of periosteum in an organ culture model towards cartilage, rich in collagen type II, using combinations of biochemical and mechanical stimuli. We hypothesize that addition of TGF-ß will stimulate chondrogenesis, whereas sliding indentation will enhance collagen synthesis. DESIGN: Periosteum was dissected from the tibiotarsus of 15-day-old chick embryos. Explants were embedded in between two agarose layers, and cultured without stimulation (control), with biochemical stimulation (10 ng/ml TGF-ß1), with mechanical stimulation (sliding indentation), or both biochemical and mechanical stimulations. Sliding indentation was introduced as a method to induce tensile tissue strain. Analysis included quantification of DNA, collagen and GAG content, conventional histology, and immunohistochemistry for collagen type I and II at 1 or 2 weeks of culture. RESULTS: Embedding the periosteal explants in between agarose layers induced cartilage formation, confirmed by synthesis of sGAG and collagen type II. Addition of TGF-ß1 to the culture medium did not further enhance this chondrogenic response. Applying sliding indentation only to the periosteum in between agarose layers enhanced the production of collagen type I, leading to the formation of fibrous tissue without any evidence of cartilage formation. However, when stimulated by both TGF-ß1 and sliding indentation, collagen production was still enhanced, but now collagen type II, while sGAG was found to be similar to TGF-ß1 or unloaded samples. CONCLUSIONS: The type of tissue produced by periosteal explants can be tuned by combining mechanical stimulation and soluble factors. TGF-ß1 stimulated a chondrocyte phenotype and sliding indentation stimulated collagen synthesis. Such a combination may be valuable for improvement of the quality of tissue-engineered cartilage.

Quality of life and depressive symptoms in patients suffering from sarcoidosis.

BACKGROUND: Apart from the disease status, chronically ill patients are confronted with stressors like dependence, limitations in mobility and physical complaints. Data on patients with sarcoidosis, however, are lacking. The aim of this study was to investigate the quality of life (QOL) and the influence of QOL factors on depressive symptoms in these patients. PATIENTS AND METHODS: Sixty-four patients with histologically proven sarcoidosis participated in this study. Significant co-morbidity was excluded. The Sickness Impact Profile (SIP) was used to determine the QOL. Depressive symptoms were measured with the Beck Depression Inventory (BDI), of which a subset of items measured cognitive symptoms, the Cognitive Depression Index (CDI). Disease status was assessed by pulmonary function parameters (FEV1, Dco), complaints and illness duration. To control for a confounding cognitive style of self-report, the Positive Affect Negative Affect Schedule (PANAS) was administered. RESULTS: The major complaint was fatigue. QOL was related to the perception of complaints, but not to the assessed disease status. In a multivariate regression 86% of the variance could be explained in BDI-scores, and 83% in CDI-scores. After controlling for demographical factors, disease status and cognitive style, QOL contributed to the regression, explaining another 17% of variance of BDI-scores as well as CDI-scores. Problems with sleeping were associated positively with depressive symptoms in general (beta = 0.38) and depressive cognitions only (beta = 0.32). CONCLUSIONS: In sarcoidosis, QOL factors were associated with depressive symptoms. These results suggest that patients with sarcoidosis may profit from attention to the psychosocial as well as the somatic aspects of this disease.