em cells and their partners, including osteoblasts and stromal cells, which provide HSCs with signals PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/22183719 for their homeostatic quiescent state. The architecture of the HSC niche is tightly controlled by a balance between the bone-forming cells, and the bone-resorbing cells . While osteoblasts derive from mesenchymal cells, osteoclasts derive from mononuclear precursors of the monocytic/macrophage lineage. Monocytes develop from hematopoietic stem cells in the bone marrow through several intermediate progenitors that restrict progressively their differentiation potential. The prevalent model for myeloid commitment implicates that progenitors pass through the common myeloid progenitor, the granulocyte/macrophage progenitor, and the macrophage/dendritic cell progenitors stages. Each of these steps is tightly regulated by the interplay between cytokine-induced signaling pathway and transcription factor activity. Monocytecolony stimulating factor, through its binding to MCSFR plays an essential role in both proliferation and differentiation of the myeloid progenitors. MCSF, and receptor activator of nuclear factor kappa B ligand, are essential for osteoclastogenesis. ERK1 Regulates the Hematopoietic Stem Cell Niches Mutational inactivation or genetic ablation of these molecules results in a lack of osteoclast differentiation and consequent defects in BM cavity formation, a condition termed osteopetrosis in which BM cavities are filled with bone. Accumulating evidence suggests that osteoclasts induce hematopoietic activity by secreting bone-resorbing enzymes which promote the mobilization of HSCs from their quiescent state. However, the influence of HSCs on their microenvironment is not well understood. A recent report demonstrated a cross-talk between HSCs and bone cells in the maintenance of both hematopoietic and bone homeostasis. The ERK MAPK kinases are major signaling actors relaying signals elicited by cytokines, morphogens or integrins. The MAPK pathway exerts pleiotropic effects on cell cycle, apoptosis and differentiation, and has 
been implicated in the control of many cellular responses. ERK activity is provided by two isoforms, named ERK1 and ERK2, that are highly similar, ubiquitously expressed and that share activators and substrates. We and others have found that the ERK pathway is specifically required for the differentiation of various hematopoietic lineages. However, no studies have reported the role of ERK1 or ERK2 in HSCs in vivo. Gene disruption has suggested specific functions for each isoform. Ablation of ERK2 induces embryonic lethality with death of the animals in utero at day 7.5, due to defects in the mesoderm and placental development. Conversely, ERK12/ 2 mice are viable, AVL-292 web fertile and present minor defects, showing that ERK1 is dispensable for mouse development and could be compensated by ERK2. So far, ERK1 has been shown to be specifically required for in vitro and in vivo adipogenesis, terminal differentiation of T lymphocytes, long-term memory and erythropoiesis. The involvement of the MAPK pathway in myeloid maturation has been implicated in several myeloid cell lines. Using ERK chemical inhibitors, Hsu et al. have shown that ERK signaling is involved in the early myeloid commitment of HSCs. On the other hand, ERK inhibitors have been reported to alter osteoclast differentiation and function. Very recently, He Y et al. reported the preponderant role of ERK1 over ERK2 isoform in controlling osteoclast differentiati