PubMed Health⌕ Search

Biomedical subjects

S Disthabanchong

Publications and source records attributed to S Disthabanchong.

3 recordsLinked to original sources
PubMed2006

Chronic metabolic acidosis alters osteoblast differentiation from human mesenchymal stem cells.

Bone histology of distal renal tubular acidosis patients showed decreased bone formation with impaired bone matrix mineralization that is not entirely explained by an alteration in the mineral balance. Data from in vitro studies suggests a direct inhibitory effect of metabolic acidosis on osteoblast function. We investigated the effects of chronic metabolic acidosis on osteoblast differentiation from mesenchymal stem cells (MSCs). Human MSCs were allowed to differentiate into osteoblasts in culture. Concentrated hydrochloric acid was added to the medium to lower the bicarbonate concentration and pH. The expression of various osteoblastic genes and proteins and bone matrix mineralization were examined. Chronic metabolic acidosis enhanced the messenger RNA (mRNA) and protein expression of early osteoblast transcription factor, runx-2, whereas inhibiting osterix and having no effect on ATF-4. The expression of type I collagen, the most abundant bone matrix protein, was increased following the same pattern of runx-2. Likewise, metabolic acidosis slightly enhanced the expression of mature osteoblastic gene, osteocalcin. Study on mineralization revealed suppressed alkaline phosphatase mRNA and enzyme activity. Despite the augmented collagen deposit in acidic culture, bone matrix mineralization was impaired. In conclusion, chronic metabolic acidosis alters osteoblast differentiation from MSCs through its diverse effect on osteoblastic genes and proteins resulting in an impairment of bone formation.

Acidosis, Renal Tubular↗
PubMed2002

Soluble IL-6 receptor levels in patients on chronic hemodialysis.

Osteitis fibrosa, a part of the spectrum of renal osteodystrophy, is characterized by high bone turnover as a result of high circulating levels of parathyroid hormone (PTH). It is well accepted that the bone resorptive effects of PTH occur, at least in part, by inducing osteoblasts to secrete cytokines that stimulate both differentiation and activation of osteoclasts. One such cytokine, interleukin 6 (IL-6), exerts its actions via the IL-6 receptor (IL-6R), which has alpha and beta subunits. The alpha subunit binds IL-6 and exists in both membrane bound and soluble forms which can interact with the signal transducing components of the receptor or beta subunits and result in the same biological effect. Abnormalities in the IL-6 system have the potential to affect bone turnover and to modulate the effects of PTH. In this regard, we examined the levels of circulating soluble IL-6 receptor (sIL-6R) and plasma intact PTH in 27 patients on hemodialysis, of whom 15 were on therapy with vitamin D compounds and 12 were vitamin D naive. The results were compared to values obtained from 9 healthy controls. Blood samples were obtained pre-dialysis and sIL-6R levels were determined using a commercially available enzyme immunoassay, which measures biologically active sIL-6R. In patients on chronic hemodialysis, plasma levels of sIL-6R were 123.4 +/- 11.01 ng/ml. In healthy controls, the levels were 99.61 +/- 11.52 ng/ml, values not significantly different from those found in dialysis patients. PTH values ranged from 7-1,709 pg/ml in patients on hemodialysis; however, there was no correlation between intact PTH levels and the levels of sIL-6R. Similarly, vitamin D therapy did not influence the levels of sIL-6R. These data indicate that using an assay which is specific for biologically active sIL-6R, the levels of this receptor in patients on hemodialysis are similar to those found in normal individuals and neither the levels of PTH nor vitamin D therapy alter this aspect of IL-6 action.

Adult↗