Building Bone: Human mesenchymal stromal cells and the identification of genes and processes in osteoblast differentiation

This thesis presents a number of novel findings in the bone biology field using a combination of bioinformatic, genomic, molecular, and proteomic approaches, and highlights the complexity of the biology and study of osteoblast differentiation. The results described within include the discovery of number of fa

Osteotropic cytokines mediate human osteoblast-like cell eicosanoid production

We have examined the effects of the cytokines tumor necrosis factoralpha (TNF), transforming growth factorbeta (TGFbeta) and the effect of cyclooxygenase inhibitor ibuprofen on prostaglandin and 15-HETE biosynthesis by normal adult human osteoblast-like (hOB) cells. In the present studies, conditioned media harvested from hOB cell cultures were assayed by eicosanoid specific EIAs to determine quantitatively the effects of cytokines on PGE2, 6-keto-PGF1alpha, PGF2alpha, PGD2, thromboxane (TXB2) and on 15-HETE biosynthesis. EIA analysis indicated that PGE2 was the predominant PG metabolite released by unstimulated hOB cells and its synthesis was increased more than other PGs in cells treated with (TGFbeta) and TNFalpha, both separately and in combination.;Thus, these studies indicate that (TGFbeta) and/or TNFalpha, modulate AA metabolism and upregulation of PGE2 synthesis elicited by these cytokines might have resulted from an increased level of the terminal PGE 2 synthases in hOB cells. (Abstract shortened by UMI.)