the NSAIDs that inhibit COX2 may affect the system must be possible important degradative pathway for anandamide and 2 arachidonoyl glycerol might require COX 2. CB2 is a Gi protein Ccoupled receptor activated by phytocannabinoids and endo, hence inhibiting stimulated adenylyl cyclase activity. CB2 is expressed in bone Aurora B inhibitor cells and Cb2 null mice show a marked age-related bone loss. CB2 particular agonists both rescue and attenuate ovariectomy induced bone loss. Service of bone marrow and CB2 stimulates osteoblast proliferation derived colony forming units osteoblastic. Here we demonstrate that selective and nonselective CB2 agonists are mitogenic in MC3T3 E1 and newborn mouse calvarial osteoblastic cultures. The CB2 mitogenic signaling depends significantly about the stimulation of Erk1/2 phosphorylation and de novo synthesis of MAP kinase Cactivated protein kinase 2 mRNA and protein. Further downstream, CB2 activation improves CREB transcriptional activity and cyclin D1 mRNA expression. The CB2 induced activation of CREB and cyclin D1 is inhibitable by pertussis toxin, the MEK Erk1/2 inhibitors PD098059 and U0126, and Mapkapk2 siRNA. These data show that in osteoblasts CB2 targets a Gi protein Ccyclin D1 mitogenic axis. Mapkapk2 protein synthesis and erk1/2 phosphorylation are critical Organism intermediates in this axis. 2011 American Society for Bone and Mineral Research. CB2 is a seven transmembrane domain receptor coupled to the inhibitory guanine nucleotide binding regulatory protein subclass of G proteins. It is triggered by endo and phytocannabinoids, therefore suppressing stimulated adenylyl cyclase activity. Unlike the neuronal CB1 cannabinoid receptor, CB2 is expressed mainly in nonneuronal cells and has no psychoactivity. In bone, CB2 is expressed in osteoblasts, osteocytes, and osteoclasts. Cb2 ATP-competitive ALK inhibitor null mice show a marked age-related bone loss, and CB2 particular agonists both attenuate and rescue ovariectomy Cinduced bone loss. Significantly, CB2 initial is mitogenic to osteoblasts in culture and increases the amount of bone marrow colony forming units osteoblastic. At least one of the endocannabinoids present in bone, anadamide, stimulates osteoblast proliferation in vitro. In mammalian cells, your family of mitogen activated protein kinases offers a key link between membrane bound receptors and changes in the pattern of gene expression. The MAP kinases are activated downstream of several different types of receptors, including serpentine G protein Ccoupled receptors, and tyrosine kinase receptors, cytokine receptors. The MAP kinases contain three subfamilies: the extracellular signal Cregulated kinases 1 and 2, c Jun N terminal kinase/stress activated kinase, and p38 MAP kinase. Further downstream, they manage numerous transcription facets that get a handle on cell growth, survival, and differentiation.