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A Littlewood

Publications and source records attributed to A Littlewood.

5 recordsLinked to original sources
PubMed1994

Expression of mRNA for IL1 beta, IL6 and TGF beta 1 in developing human bone and cartilage.

Using in situ hybridization, we investigated the expression of mRNA for interleukin-1 beta (IL1 beta), interleukin-6 (IL6), and transforming growth factor-beta-1 (TGF beta 1) in sections of developing bone in human osteophytes. The expression was related to the cellular activity of alkaline phosphatase to aid in the identification of pre-osteoblast populations. IL1 beta mRNA was localized in active osteoblasts within distinct areas of intramembranous ossification. However, the expression was sporadic and appeared to occur at a specific stage of the osteoblast life cycle. There was no IL1 beta mRNA expression in any cell types during endochondral ossification. IL6 mRNA expression was located within pre-osteoblasts and in newly differentiated and matrix-secreting osteoblasts; expression was absent or reduced in flattened, inactive osteoblasts. Weak or no IL6 expression was observed in chondroblasts and chondrocytes, respectively. However, there was a close association between IL6 mRNA expression and the differentiation of mesenchymal cells into osteoblasts. TGF beta 1 expression was localized to osteoblasts apposed to bone or cartilage matrix; the intensity of expression correlated with matrix secretion. Chondroblasts and chondrocytes expressed lower but significant levels of TGF beta 1 mRNA; the expression was lost with the progression to calcifying cartilage. The three cytokines studied were differentially expressed both temporally and spatially, suggesting different roles for each in osteoblast and chondrocyte function.

Alkaline Phosphatase↗
PubMed1993

Expression of osteopontin mRNA by osteoclasts and osteoblasts in modelling adult human bone.

Over recent years several non-collagenous matrix proteins of bone have been isolated and characterized. One of these proteins, osteopontin, has been shown to be synthesized by osteoblasts and deposited in the bone matrix where it is thought to bind to hydroxyapatite. However much of the functional evidence is circumstantial, and the precise function of osteopontin has not been fully elucidated. We have used in situ hybridization techniques to investigate the expression of osteopontin mRNA in a variety of human bone tissues. Cryostat sections of human osteophyte and osteoclastoma tissue were hybridized with an antisense RNA probe for osteopontin. Sense transcripts were used as a negative control to assess non-specific binding. There was a very distinct pattern of osteopontin mRNA expression in these tissues. Plump osteoblasts adjacent to the osteoid matrix expressed high levels of osteopontin mRNA, whilst flattened osteoblasts demonstrated weaker expression. The most striking feature of osteopontin mRNA expression was the high levels detected in osteoclasts. Osteoclasts in resorption lacunae and those distant from resorption sites both expressed osteopontin mRNA, suggesting that attachment was not a prerequisite for osteopontin expression. A population of mononuclear cells in resorption lacunae was also observed to express high levels of osteopontin mRNA. The whole population of osteoclasts in the osteoclastoma tissue expressed high levels of osteopontin mRNA, indicating that expression is not restricted to osteoclasts involved in bone resorption. This study confirms that human osteoblasts are capable of synthesizing osteopontin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Production of tumor necrosis factor by human osteoblasts is modulated by other cytokines, but not by osteotropic hormones.

Human osteoblast cultures derived as out-growths from trabecular bone released tumor necrosis factor (TNF alpha) upon stimulation of the cells with human recombinant interleukin 1 (IL1; 10(-13)-10(-11) M), human recombinant granulocyte-macrophage colony-stimulating factor (100-1000 U/ml), and bacterial lipopolysaccharide (5-500 ng/ml). The osteotropic hormones 1,25-dihydroxyvitamin D3, PTH, and calcitonin had no effect on TNF production. The TNF released by the osteoblasts was identified as TNF alpha, using a specific anti-TNF alpha monoclonal antibody to neutralize its activity. Immunohistochemical staining of the cells using the same antibody revealed that all of the cells in the cultures were capable of producing TNF alpha, including those that also expressed alkaline phosphatase activity. Immunoreactive protein could be detected in the perinuclear region when cells were cultured in the presence of monensin, suggesting accumulation of newly synthesised protein in the Golgi apparatus. These results suggest that human osteoblasts, which have been shown previously to respond to TNF alpha, can synthesize and release TNF in response to IL1 and granulocyte-macrophage colony-stimulating factor. TNF may, therefore, not only have a pathological role in conditions of chronic inflammation, but also may act as a local paracrine or autocrine regulator of osteoblast function.

Calcitonin↗