Anti-OSMR (aa 185-196) polyclonal antibody

Bone resorption by osteoclasts and bone formation by osteoblasts are tightly coupled processes implicating factors in TNF, bone morphogenetic protein, and Wnt families. In osteoimmunology, macrophages were described as another critical cell population regulating bone formation by osteoblasts but the coupling factors were not identified. Using a high-throughput approach, we identified here Oncostatin M (OSM), a cytokine of the IL-6 family, as a major coupling factor produced by activated circulating CD14+ or bone marrow CD11b+ monocytes/macrophages that induce osteoblast differentiation and matrix mineralization from human mesenchymal stem cells while inhibiting adipogenesis. Upon activation of toll-like receptors (TLRs) by lipopolysaccharide or endogenous ligands, OSM was produced in classically activated inflammatory M1 and not M2 macrophages, through a cyclooxygenase-2 and prostaglandin-E2 regulatory loop. Stimulation of osteogenesis by activated monocytes/macrophages was prevented using neutralizing antibodies or siRNA to OSM, OSM receptor subunits gp130 and OSMR, or to the downstream transcription factor STAT3. The induced osteoblast differentiation program culminated with enhanced expression of CCAAT-enhancer-binding protein d, Cbfa1, and alkaline phosphatase. Overexpression of OSM in the tibia of mice has led to new bone apposition with no sign of bone resorption. Two other cytokines have also a potent role in bone formation induced by monocytes/macrophages and activation of TLRs: IL-6 and leukemia inhibitory factor. We propose that during bone inflammation, infection, or injury, the IL-6 family signaling network activated by macrophages and TLR ligands stimulates bone formation that is largely uncoupled from bone resorption and is thus an important target for anabolic bone therapies. STEM CELLS 2012; 30:762772

IL-31, predominantly produced by CD45RO + CLA + Th2 cells, plays an important pathogenetic role in pruritic skin diseases like atopic dermatitis. As tumor cells in S,zary syndrome (SS) and Mycosis fungoides (MF) possess similar immunophenotypes and the conditions mentioned are often associated with pruritus, the analysis of the IL-31 pathway in MF/SS patients is of interest. Serum samples from the peripheral blood of 23 patients and 17 controls were analyzed for IL-31 abundance and correlated with disease stage and pruritus. Furthermore IL-31-, IL-31 receptor alpha (IL-31R alpha)- and Oncostatin M receptor beta (OSMR beta)-mRNA expression was measured in blood tumor cells from SS patients, memory T-cells from controls and lymphoma cell lines. Serum IL-31 levels were low but differed between groups with no or strong pruritus. Expression of IL-31 was detectable at low levels in cell lines, but not in the tumor cells of SS patients. Stimulation with PMA/ionomycin led to indiscriminate expression in peripheral blood tumor cells and control T-cells. IL-2-stimulation resulted in expression only in 9/11 patient samples. IL-31R alpha-expression was detectable in 10/10 cell lines, 8/15 peripheral blood samples from SS patients, and 4/10 controls; whereas, OSMR beta mRNA was detectable in 4/10 cell lines, but only one patient and control sample. The results of our analyses regarding serum levels and receptor expression do not suggest a central role of IL-31 in MF/SS pathogenesis. However, the results of IL-2 stimulation as well as the increased IL-31 levels in patients with strong pruritus offer a rationale for therapeutic approach in this subset of patients.