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Background:The mechanisms whereby ␣5␤1 integrin triggers osteogenesis are poorly understood. Results: CRRETAWAC-mediated ␣5␤1 integrin priming promotes osteoblast differentiation via PI3K/Wnt/␤-catenin signaling independently of the RGD-like REET sequence. Systemic delivery of the ␣5␤1 integrin-priming peptide improved long bone microarchitecture in senescent osteopenic mice. Conclusion: Wnt signaling mediates osteoblast differentiation induced by peptide-mediated ␣5␤1 integrin priming. Significance: A novel mechanism underlying ␣5␤1 integrin-mediated osteoblast differentiation is provided.

1 Several compounds, mainly opioid agonists such as methadone, are currently used for long term medication of heroin addicts. Nevertheless, these maintenance treatments have the disadvantage to induce a dependence to another opiate. As interactions between opioid and cannabinoid systems have been demonstrated, the ability of the CB 1 antagonist, SR141716A to reduce morphine-induced addiction was investigated. 2 The eects of SR141716A on the rewarding responses of morphine were evaluated in the place conditioning paradigm. No signi®cant conditioned preference or aversion were observed after repeated treatment with the CB 1 antagonist alone. However, SR141716A was able to antagonize the acquisition of morphine-induced conditioned place preference. 3 SR141716A was co-administered with morphine for 5 days, and the withdrawal syndrome was precipitated by naloxone administration. A reduction in the incidence of two main signs of abstinence: wet dog shakes and jumping was observed while the other were not signi®cantly modi®ed. In contrast, an acute injection of the CB 1 antagonist just before naloxone administration was unable to modify the incidence of the behavioural manifestations of the withdrawal, suggesting that only chronic blockade of CB 1 receptors is able to reduce morphine-induced physical dependence. 4 Several biochemical mechanisms could explain the reduction of opioid dependence by CB 1 antagonists. Whatever the hypotheses, this study supports the reported interaction between the endogenous cannabinoid and opioid systems, and suggests that SR 141716A warrants further investigations for a possible use in opioid addiction.