Other cytokines/bone regulatory components in peripheral and bone marrow plasma Along with sclerostin, we also measured levels of a number of other cytokines/bone regulatory components for potential regulation by estrogen treatment in vivo (Table five). Levels of yet another Wnt antagonist, DKK1, have been comparable in manage and estrogen-treated women in peripheral and bone marrow plasma. Plasma serotonin, RANKL, and adiponectin levels had been also related in manage and estrogen-treated women in peripheral and bone marrow plasma; there was a trend (P = 0.095) for OPG levels to become reduce in estrogen-treated girls in peripheral, but not bone marrow, plasma. Extra factors measured in bone marrow plasma only (oxytocin, TNF, IL-1, IL-6) did not differ in between the manage and estrogen-treated girls.NIH-PA Author HDAC4 Purity & Documentation Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptBone. Author manuscript; accessible in PMC 2012 August 1.M der et al.PageComparison of bone marrow versus peripheral plasma levels of cytokines/bone regulatory factors For the elements exactly where we assessed each bone marrow and peripheral plasma levels, we compared these levels in all subjects combined (Table 6). As shown, bone marrow plasma sclerostin and OPG levels were drastically higher than peripheral plasma levels; by contrast, peripheral plasma serotonin and adiponectin levels were considerably higher than bone marrow plasma levels. DKK1 and RANKL levels didn’t differ in the two compartments.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptDiscussionOur work provides “proof of concept” regarding the possible utility of bone marrow lin-/ Stro1+ osteoprogenitor cells as a novel tool to study metabolic bone ailments. Stro1 is usually a cell surface marker which is expressed on early progenitor cells that express bone-related genes but low levels of collagen; as such, these cells probably represent early osteoblast progenitors that respond to estrogen with an attenuation in proliferation, constant with preceding data in mice [2]. The up-regulation of mRNAs for adhesion molecules that we observed may serve to anchor these progenitor cells to web pages of bone remodeling. Furthermore, the constant suppression of sclerostin by estrogen in peripheral blood and bone marrow plasma make it a possible candidate for mediating effects of estrogen on bone metabolism in humans. As expected, remedy of postmenopausal girls having a physiological dose of estradiol for four months led to a important decrease in bone resorption markers with a coupled lower in bone formation markers. Despite substantial information on effects of estrogen on bone turnover markers and bone mineral density in humans [24], there is little or no information available in humans on direct effect of estrogen on the bone marrow progenitor cells or active osteoblasts on bone surfaces. The study by Di Gregorio employing a mouse model demonstrated that estrogen acts in vivo and in vitro to attenuate osteoblast precursor self-renewal by about 50 [2]. Similarly, in our study the human bone marrow lin-/Stro1+ osteoprogenitor cells expressed considerably decrease levels of proliferation genes compared to girls not treated with estrogen. Collectively, the prior mouse [2] and now our human data indicate that estrogen leads to a decrease in proliferation of osteoblast progenitor cells. We also discovered a substantial upregulation of adhesion molecules by the GSEA/O’Brien umbrella cluster tests and, in specific, upregulation of JAK3 web N-cadheri.
