Signaling through BMP proteins is regulated by either extracellular antagonists such as Noggin and Gremlin or by intracellular inhibitors, e.g. AH 6809 inhibitory SMAD proteins or nuclear MAB21L2, a recently discovered BMP4 inhibitor. Depending on coreceptors WNT signaling can be divided into canonical and non-canonical pathways. Canonical signaling is induced by binding of WNT ligands to the receptors of the Frizzled family and LRP5/6 coreceptors, which results in activation of WNT-specific gene transcription by stabilization and nuclear translocation of b-Catenin. Non-canonical WNT signaling is transduced through FZD and ROR2/RYK coreceptors, which leads to the activation of G-protein or Ca2+ -dependent cascades. In MSC canonical signaling through WNT2, WNT3 or WNT3a induces proliferation and keeps the cells in an undifferentiated state, whereas non-canonical signaling, e.g. by WNT5a, WNT5b or WNT11, supports osteogenesis. The osteocyte-specific factor Sclerostin was described as an inhibitor of canonical WNT signaling, whereas there is ongoing discussion about its putative inhibitory effect on BMP signaling. Sclerostin leads to reduced bone formation and loss of function mutations are responsible for the high bone mass syndromes Van Buchem disease and sclerosteosis. A neutralizing antibody against Sclerostin is a new, upcoming therapeutic treatment for osteoporosis. Intermittent treatment with parathyroid hormone is another therapeutical approach for osteoporosis and activates the third major signaling pathway in bone regeneration. However, continuous activation of PTH receptor has negative effects on bone homeostasis because subsequently enhanced RANKL expression on maturing osteoblasts stimulates osteoclast formation and bone resorption. Interestingly, the genetic loci of proteins involved in the signaling pathways mentioned above, e.g. LRP5, LRP4, Sclerostin, PTH, BMPs or BMP receptor BMPR1B, have already been linked to the polygenetic nature of primary osteoporosis by wholegenome association studies and meta-analyses. Besides genetic predisposition, advanced age is another strong risk factor for developing osteoporosis with adult stem cells being the restrictive parameter for unlimited tissue regeneration. In vitro, cells exhibit limited dividing capacity and enter replicative senescence, a state of irreversible G1 phase arrest, after about 50 population doublings. It is caused by multiple factors like telomere shortening, oxidative stress, deficiencies in DNA repair and epigenetic changes. Currently it is still controversial, whether clock-driven, organismic aging is caused by the loss of selfregeneration due to replicative senescence of stem cells or by extrinsic environmental factors. The impact of presumptive deficiencies of hMSC in 1-BCP elderly, osteoporotic patients has not been studied intensely yet and to our knowledge changes at the gene expression level have not been examined before.